Απ: ΑΔΕΝΟΣΙΝΗ και Hair regrowth
παραθέτω εδώ μια έρευνα η οποία συνδέει την μινοξ με την Αδενοσίνη (ATP)
όπως όλοι λίγο πολύ ξέρουμε η μινοξ επιδράει και ανοίγει τα ATP sensitive potassium channels '' ευαίσθητα στην τριφοσφωρική Αδενοσινη κανάλια καλίου'' η διόδους καλίου ( potassium channels)
η παρακάτω έρευνα αναφέρει οτι οι θύλακες διαθέτους 2 ειδών ευσαίσθητους στην αδενοσίνη διόδους καλίου εκ των οποίων
ΜΟΝΟ στον ένα επιδράει η μινοξιδίλη ....
The FASEB Journal • Research Communication
Human hair follicles contain two forms of ATPsensitive
potassium channels, only one of which is
sensitive to minoxidil
Katie Shorter,* Nilofer P. Farjo,† Steven M. Picksley,* and Valerie A. Randall*,1
*Department of Biomedical Sciences, University of Bradford, Bradford, UK; and †Farjo Medical
Minoxidil stimulates small vellus follicles, producing
tiny, virtually colorless hairs to produce longer, more
visible hairs (8). Throughout life follicles pass through
repeated cycles of growth (anagen), regression (catagen),
and rest (telogen), during which the follicle
replaces the hair with a similar one or one that differs
in size and/or color, in line with changes such as sexual
development or season (1). The marked variations in
hair length seen on the human body reflect differences
in the anagen period; anagen ranges from 2 to 5 yr for
long scalp hair to a few weeks for short finger hairs,
whereas the growth rate is very similar everywhere (9,
10). In androgenetic alopecia, androgens inhibit scalp
follicles producing normal visible terminal hairs, causing
them to miniaturize and produce vellus hairs with a
much shorter anagen period (11). Systemic minoxidil
causes hypertrichosis including increased hair growth
on the forehead, eyebrow thickening, and diffuse
growth on the back and limbs in about 3 months in
60–80% of adults (12, 13), whereas topical minoxidil
treatment for androgenetic alopecia causes a rapid
increase in hair weight (14) and hair density (15).
These results suggest that minoxidil is recruiting telogen
follicles into anagen and then producing a longer
hair by increasing the length of the actively growing
phase of the anagen hair cycle.
Minoxidil, or rather its active metabolite minoxidil
sulfate (16), diazoxide, and pinacidil reduce blood
pressure by opening
KATP channels in vascular smooth
muscle, causing the musculature to relax (17, 18).
Because minoxidil and some other, but not all, KATP
channel-opening drugs, including
diazoxide (19) and
pinacidil (20), can cause unwanted hair growth despite
their diverse structures, opening of KATP channels is
probably part of the action of minoxidil, although
whether the target is the vasculature or the follicle’s
cells is unclear. Topical minoxidil increased scalp
blood flow in balding men when applied at 5% (21) but
not 3% doses (22) and increased fenestrations in rat
follicular capillaries (23), implicating actions via the
vasculature. However, clinical effects are seen with even
2% minoxidil (6) and not all vasodilators stimulate hair
growth, so follicular responses seem more probable.
KATP channels play key physiological roles in many
tissues with significant clinical implications (24–26),
but whether they are present in the follicle and, if so,
what role(s) they may have is unknown.
ας δούμε τί είναι τα περίφημα kATP channels
KATP channels are
protein channels that control the
flow of potassium ions across cell membranes in many
tissues, e.g., heart (24, 26, 27). Recent research has
yielded much information about the structure and
function of these channels. Physiologically they are
regulated
by intracellular levels of nucleotides, e.g.,
ATP and ADP, thereby linking the electrical activity of
a cell’s membrane to its metabolism, controlling diverse
cellular functions such as pancreatic insulin secretion
or providing protection against heart ischemia
(25–27). A diverse group of compounds can also bind
to KATP channels causing them to open or close; drugs
used therapeutically include
sulfonylureas, e.g.,
glibenclamide
and
tolbutamide, which close pancreatic channels
to help control type 2 diabetes, and
nicorandil, a
KATP channel opener used for angina pectoris
KATP channels consist of eight subunits arranged in
two rings (Fig. 1). The inner ring of four inwardly
rectifying K channel (Kir6.X) subunits forms the pore
through which potassium ions pass, whereas the outer
ring comprises four regulatory sulfonylurea receptor
(SUR) subunits that can alter channel activity in response
to intracellular nucleotides or extracellular
drugs (26). Both subunit classes are necessary to form a
functional channel (28, 29). The pore subunit, Kir6.X,
is found in two forms, Kir6.1 and Kir6.2, which combine
with a sulfonylurea subunit. These include two
isoforms of SUR, SUR1 and SUR2; SUR2 also has two
splice variants, SUR2A and SUR2B
περνάμε σε ακαταλαβίστικα mumbo jumbo κος βοήθα
The subunit
combinations present in specific tissues vary, e.g.,
pancreatic cells and neurons have Kir6.2/SUR1 channels,
whereas cardiac muscle has Kir6.2/SUR2A channels,
nonvascular smooth muscle has Kir6.2/SUR2B
channels, and vascular smooth muscle has Kir6.1/
SUR2B channels (25–27). These differences mean that
drugs have varying abilities to affect KATP channels in
different tissues depending on their type of sulfonylurea
receptor (25, 27).
Therefore, elucidating what
forms, if any, are present in human follicles could not
only improve our understanding of hair follicle function
but also facilitate the development of novel therapies
better adapted to promote hair growth or more
precisely focused on other tissues, avoiding unacceptable
hair growth side effects.
One reason that the role of potassium channels and
minoxidil is still unclear is the confusing in vitro results
to date.
Studies assessing the effects of minoxidil on
cultured follicles and cells from several species have
produced variable, often conflicting, results (8, 30).
Initial experiments with neonatal mouse whisker follicles
showed stimulation with minoxidil and some other
KATP channel openers (31), but channel blockers,
tolbutamide and glyburide, did not prevent this stimulation
(32). Unfortunately, earlier experiments were
often confused by adding serum that inhibits follicle
growth (33) and/or
streptomycin,(οκ αυτό είναι αντιβίωση
)
which can interfere
with the action of minoxidil (34). Using serum- and
streptomycin-free conditions, we recently showed that
minoxidil and diazoxide stimulated cultured isolated
deer hair follicle growth and that KATP channel inhibitors,
tolbutamide and glibenclamide, blocked their
effects (30). T
his finding strongly supports a mechanism
via direct effects of minoxidil on KATP channels
within follicles themselves, as cultured follicles have no
vascular supply
The effects of minoxidil on human follicles in vitro
are less clear-cut.
Minoxidil at low concentrations stimulated
human follicles, an effect attributed to attenuation
of the serum inhibitory effect, whereas high concentrations
caused inhibition (33). Recently a carefully
conducted large study involving follicles cultured without
serum or streptomycin detected no effect of minoxidil
(35). In contrast, small studies reported that
minoxidil increased follicle growth (36, 37) or [3H]thymidine
incorporation, indicating cell division (38).
Investigations involving cultured components of human
follicles are also contradictory. Both follicular
dermal papilla cells (36, 39, 40) and epidermal keratinocytes
(41) responded to minoxidil in vitro, but potassium
channels were not detected in either dermal
papilla or outer root sheath cells (follicular keratinocytes)
using patch-clamp techniques to investigate potassium
ion transport across their membranes
With the aims of establishing whether or not human
hair follicles contain KATP channels, we used organ
culture, molecular biological, and immunohistological
approaches to investigate scalp follicles from nonbalding
regions of healthy individuals. Initially, we investigated
whether KATP channel regulators could alter hair
follicle cycle activity in culture by observing follicle
bulbs carefully every day to see any effects on the length
of anagen, as this seems to be the main way in which
minoxidil alters hair size. Human follicles were cultured
for the first time in the presence of the KATP
channel blocker, tolbutamide, to see if this would
inhibit hair follicles and/or oppose any effects of
minoxidil. Because Han et al. (36) reported increased
growth in cultured follicles from three young men,
rather than the older donors frequently studied, using
high concentrations of minoxidil, we cultured individual
anagen scalp hair follicles from young adults in
serum- and streptomycin-free medium with similar high
concentrations of minoxidil. These concentrations are
believed to represent those reaching the follicle in vivo
after topical treatment with 5% minoxidil (35, 36).
Because phenol red (phenolsulfonphthalein), the pH
indicator regularly added to standard culture media,
may interfere with agents that modulate potassium
channels (A. G. Messenger and M. P. Birch, personal
communication, 1999) and commonly contains a number
of lipophilic impurities generated during its synthesis
(43), the follicular response to potassium channel
modulators was also examined in parallel experiments
in the absence of phenol red.
We also investigated the expression of genes for the
various subunits of KATP channels using reverse transcriptase
(RT) -polymerase chain reaction (PCR) to
determine whether KATP channel genes are expressed
in human follicles. The mRNA coding for genes actively
being expressed in the lower part of individually isolated
scalp anagen hair follicles from healthy younger
adults was translated into cDNA before amplification by
PCR using specific primers to identify genes for KATP
channel subunits. RT-PCR allows detection of genes
expressed at low levels in small samples of isolated hair
follicles owing to extensive amplification.
To identify which genes were expressed in individual
parts of the hair bulb, the regulatory dermal papilla,
the epithelial hair matrix, which divides to form the
hair and inner root sheath, and the dermal, or connective,
tissue sheath, which surrounds the follicle, were
isolated by microdissection and analyzed by RT-PCR.
To confirm the presence of the actual proteins and
check their location in the hair bulb, immunohistochemistry
was also carried out on frozen scalp sections.
MATERIALS AND METHODS
Skin samples
Human scalp skin from nonbalding areas was obtained from
healthy individuals undergoing elective cosmetic surgery operations;
appropriate ethical committee approval was obtained,
and donors provided written consent. For the organ
culture investigations donors were young adults (1 woman
and 12 men aged between 21 and 40 yr). Samples were
collected into sterile tubes containing basic culture medium:
William’s E medium containing 10 g/ml phenol red (Sigma-
Aldrich Ltd., Dorset, UK) supplemented with 10 g/ml
insulin (Sigma-Aldrich Ltd.), 10 ng/ml hydrocortisone (Sigma-
Aldrich Ltd.), 2 mM l-glutamine (Life Technologies, Inc.,
Paisley, UK), and 10 U/ml penicillin (Sigma-Aldrich Ltd.).
They were transported on ice and stored at 4°C until hair
follicles were isolated within 24 h of removal.
For the molecular biological investigations skin samples
collected from occipital and parietal regions of three men
(aged 26, 33, and 41 yr) and two women (aged 52 and 65 yr)
were placed individually into sterile tubes containing the RNA
stabilization solution, RNAlater (Sigma-Aldrich Ltd.) to inhibit
RNases. They were transported on ice and kept at 4°C
overnight to allow tissue penetration by RNAlater.
Isolation of hair follicles and hair bulb components
Isolation of hair follicles and hair bulb components
Human hair follicles in the growing phase, anagen, were
microdissected individually from each skin sample under a
Leica MZ8 dissecting microscope using sterile equipment and
plasticware. Each sample was transferred to a Petri dish
containing sterile PBS (Oxoid, Hampshire, UK) for organ
culture or RNAlater at 4°C for further molecular biological
studies. The sample was cut at the level of the dermalsubcutaneous
fat interface using a scalpel blade. Intact anagen
follicles were then gently pulled from the subcutaneous
fat using fine forceps, taking care not to damage them.
Isolated follicles were pooled into a fresh dish of cold PBS or
RNAlater, and each follicle was gently cleaned of any attached
dermis or subcutaneous fat using 27.5-gauge sterile syringe
needles. Special care was taken to ensure that the follicles
were not damaged during isolation as undamaged follicles
are essential for successful culture (44). To localize the gene
expression in the hair bulb, bulb components, the epithelial
matrix, dermal sheath, and dermal papilla, were microdissected
from 120 follicles from each individual before separate
total RNA isolation. Components from three individuals were
processed separately.
Hair follicle organ culture
Isolated human anagen hair follicles were carefully transferred
to an individual well of a 24-well plate (Corning
Glassworks, Corning, NY, USA) containing 1 ml of William’s
E medium supplemented as described below. At least six hair
follicles were cultured in each type of medium for each
individual. Follicles were maintained free-floating at 37°C in
an atmosphere of 5% CO2 and 95% air in a humidified
incubator. Medium was changed every 3 days, taking care not
to damage the follicles
Basic culture medium (see Skin Samples) was supplemented
with either minoxidil (1 mM; dissolved into a stock solution of
William’s E medium; Sigma-Aldrich Ltd.), tolbutamide [1
mM; dissolved into a stock solution of dimethyl sulfoxide
(DMSO); Sigma-Aldrich Ltd.] or both minoxidil (1 mM) and
tolbutamide (1 mM). Stock solutions of minoxidil and tolbutamide
were dissolved using a sonicating water bath (Dawe
Instruments Ltd., Middlesex, UK). Control medium was prepared
without minoxidil or tolbutamide supplements, but the
vehicle (0.001% DMSO) was added to each medium. All
culture media were sterile-filtered (0.2 m; Sarstedt, Nu¨mbrecht,
Germany) before use.
To investigate any effect of factors in the phenol red,
human hair follicles were also grown in the presence of
potassium channel modulators in phenol red-free William’s E
medium (Sigma-Aldrich Ltd.). The supplements added to the
phenol red-free William’s E media for these experiments
were prepared as for the normal media described above. To
investigate whether growing human hair follicles in a more
basic medium would enable minoxidil to have a stimulatory
effect, follicles were also cultured in basic culture medium
without insulin and hydrocortisone.
Assessment of hair follicle growth in culture
Hair follicles were assessed for morphology of the follicle
bulb every 24 h for 10 days, using a Leitz Labovert inverted
microscope (Leitz Labovert FS, Wetzlar, Germany). Hair
follicles that had not grown after 3 days were classed as
nonviable and excluded. Follicles were photographed daily
using a Nikon Coolpix 4500 digital camera (Nikon, Tokyo,
Japan). The mean percentage of follicles in anagen per
person for each treatment was determined before calculation
of the sample mean. Data from each experimental group
were analyzed for normal distribution using the Kolmogorov-
Smirnov test. The effect of the different treatments on the
percentage of follicles in anagen with time in culture was
analyzed by a two-factor, within-subjects analysis of variance
using the SPSS statistical analysis program (SPSS Inc., Chicago,
IL, USA). If the sample means of the different experimental
groups differed significantly (P0.05), selected experimental
group means were compared using a Student’s
paired t test with Sidak’s correction for multiple comparisons.
The effect of phenol red and minoxidil in the absence of
insulin and hydrocortisone on the numbers of follicles in
anagen was compared at day 9 using an unpaired Student’s t
test.
τέλος πάντων όλη η υπόλοιπη έρευνα εδώ
http://www.fasebj.org/content/22/6/1725.full.pdf+html
RESULTS
Potassium channel regulators affected human hair
follicle growth in organ culture
Human hair follicles were able to synthesize new hair in
culture, which increased regularly in length (Fig. 2A).
After 2 days there was a gradual decline in the numbers
of hair follicles remaining in anagen to 70% at day 9
(Fig. 3). When anagen was ending, follicles showed
catagen-like changes in the hair bulb region with
pigmentation ceasing and the hair fiber moving upward,
losing contact with the dermal papilla, which
became rounded up into a ball of cells (Fig. 2B).
Minoxidil had no effect on this aspect of hair growth,
whereas the KATP channel closer, tolbutamide, significantly
decreased the number of growing follicles
(P0.01); only 45% remained growing after 9 days of
culture. However, when minoxidil and tolbutamide
were incubated together, there was no inhibition of
anagen (Fig. 3).
Phenol red in the media had no effect on human hair
follicle responses to KATP channel regulators
When follicles were grown in medium without phenol
red for 9 days, they continued to grow, but the rate of
growth was reduced; they reached only 1.25 mm in
length in 9 days, compared with almost 2 mm in normal
medium (Fig. 2C). However, both media types maintained
the same proportions of follicles in anagen (Fig.
4A). Importantly, if the percentages of growing follicles
were compared when grown in the presence of KATP
channel regulators, the pattern remained the same in
the absence of phenol red (Fig. 4B); tolbutamide again
inhibited the number of follicles in anagen in the
absence of phenol red (P
0.01), and coincubation
with minoxidil was still able to overcome this inhibition
Minoxidil prolongs anagen in insulin- and
hydrocortisone-free medium
When follicles were cultured in the absence of insulin
and hydrocortisone, they entered a catagen-like state
very rapidly (Fig. 5). However, the addition of minoxidil
(1 mM) to this medium increased the numbers of
follicles in anagen, returning them to only slightly
lower levels than those cultured in normal medium
(compare Figs. 3 and 5). A lower concentration of
minoxidil (10 M) caused less stimulation. Tolbutamide
(1 mM) had no effect on its own, but prevented
any stimulation when combined with 1 mM minoxidil.
Hair follicles express the genes for several KATP
channel subunits
Total and poly(A)RNA were successfully extracted
from microdissected scalp follicles, and the quality of
each individual’s cDNA was confirmed by PCR with
primers for -actin, a highly expressed cytoskeletal
protein, producing bands of the expected size, 838 bp
(data not shown). Because KATP channels cannot function
without Kir6.X subunits to form the pore, the
expressions of Kir6.1 and Kir6.2 genes were examined.
The predicted sized bands of 336 and 301 bp, respectively
(48), were seen after electrophoresis in all samples
(Fig. 6), indicating gene expression of pore components
for at least two channel types. If KATP channels
were present in human follicles, a SUR2 type, which
could respond to minoxidil, would be expected (27).
Therefore, SUR2 genes were examined using a single
pair of primers that would identify both SUR2A and 2B,
distinguishing between their expression, as these are
different splice variants from one gene (47). A band for
SUR2B, at 312 bp, but not for SUR2A, was seen in all
samples (Fig. 6). The ability of these primers to also
identify SUR2A was confirmed using deer skeletal muscle
(data not shown). To determine whether SUR1
receptors were also present, cDNA samples were amplified
with primers specific for SUR1 (46), giving bands
at 291 bp (Fig. 6). PCRs and agarose gel electrophoresis
were repeated using specialized conditions for sequencing;
these verified all genes against their relevant human
sequences in GenBank.
Human hair bulb tissues express the genes for
different KATP channels
It was difficult and time consuming to isolate the
various hair follicle bulb components by microdissection,
but sufficient good-quality cDNA was obtained
when 120 follicles were used from each individual. The
lowest yields came from the dermal papillae. The
dermal papilla and dermal sheath samples all expressed
SUR2B and Kir6.1, but not SUR 1, SUR2A, or Kir6.2
(Table 1). In contrast, the hair matrix samples expressed
SUR1 and Kir6.2 but not SUR2A SUR2B, or
Kir6.1 (Table 1)
Immunohistochemical localization of KATP channel
subunits in human hair follicle bulbs
SUR2B protein expression was seen in the dermal
papilla and dermal sheath but not in the epithelial
cells of the hair bulb matrix (Fig. 7D); strong staining
was seen around the basement membrane surrounding
the dermal papilla and weaker staining in the
cells of the dermal papilla and dermal sheath. No
similar staining was seen at the dermal-epidermal
junction (Fig. 7). In contrast, there was no staining in
the dermal papilla or dermal sheath with the antibody
to SUR1, but this antibody did stain the hair
matrix epithelial cells (Fig. 7B). The antibody to
SUR2A did not stain any area of the hair bulb or the
epidermis (Fig. 7C).
Kir6.1 expression was distributed very similarly to
that of SUR2B, with strong expression in the papilla
basement membrane and weaker staining of dermal
papilla and dermal sheath cells; there was no staining in
the matrix (Fig. 7E). The antibody to Kir6.2 stained the
matrix cells but not the dermal papilla or dermal
sheath (Fig. 7F). No similar staining was seen in the
dermal-epidermal junction with either Kir6.1 or Kir6.2
antibodies (Fig. 7).
These results are very exciting. They demonstrate a
biologically relevant shortening of anagen by a KATP
expression in hair bulb components demonstrated the presence of
two different types of KATP channels
interfere with minoxidil action (34). Possible interference
with the effects of KATP channel regulators by
phenol red was investigated by parallel experiments in
the absence of this routinely used pH indicator, but the
percentage of follicles in anagen under the KATP channel
modulators remained the same (Fig. 4). Presumably,
the stimulation of follicular growth in phenol red
media observed here and in red deer studies (30) is due
to impurities in the phenol red; substances reported
have shown estrogenic, cytotoxic, and cellular Na and
K homeostasis effects (reviewed in ref. 30). However,
phenol red had no effect on the percentage of follicles
in anagen nor the responses to either of the KATP
channel modulators used here; similarly, growth rates
of human follicles in response to minoxidil (35) or
deer follicles in response to minoxidil and tolbutamide
(30) were not altered by phenol red. It seems that
further investigations into the effects of KATP channel
regulators can be appropriately performed in normal
phenol red medium. However, the need for improved
hair growth promoters means that identifying the stimulating
impurities in phenol red merits further investigation.
Tolbutamide inhibited anagen in the presence and
absence of phenol red; i.e., the KATP channel blocker
caused an in vitro reduction of anagen length in a total
of 11 young (aged 40 yr or younger) adults (Figs. 3 and
4). If this effect was transcribed to the in vivo situation,
it would result in a shorter hair being formed. Of
interest, tolbutamide has been reported to cause human
hair loss (51) and was patented in 2007 (US patent
7160921, issued on September 2, 2007) for use as a hair
removal agent. The effect of tolbutamide was also
prevented in both conditions by simultaneous administration
of minoxidil, a KATP channel opener, indicating
an action via KATP channels within the follicle.
Minoxidil would be predicted to prolong anagen in
cultured follicles from its effect of increasing anagen in
vivo, but no effect on anagen was seen over 9 days.
However, the ability of minoxidil to prolong anagen
against the shortening caused by the potassium channel
blocker, tolbutamide, does reflect in vivo actions of
KATP channel openers in altering anagen length. The
conditions used here were designed to replicate those
of Han et al. (36) who reported increased length with
100 M and 1 mM, but not 10 M, in follicles from
three young men. Our observations do not support age
or dosage as being responsible for this unusual positive
response to minoxidil in vitro. It is possible that the
large scalp follicles normally used for culture studies
have little spare capacity to respond to minoxidil in
such a supportive medium. This group also recently
showed that when occipital follicles from two young
men were allocated into four groups depending on
their in vivo growth rate, only those growing fastest in
vivo showed a significant increase in length when incubated
with minoxidil (37). They suggested that faster
growing follicles indicated a different earlier substage of
anagen, which would be more sensitive to minoxidil.
Although minoxidil had no effect on anagen length
on its own, the inhibitory effect of the KATP channel
blocker, tolbutamide, and its neutralizing by minoxidil
suggest that KATP channels in human follicles were fully
open in these standard human follicle culture conditions
(33). These differ from the more basic conditions
without insulin or hydrocortisone used for deer follicles,
in which KATP channel regulators had the expected
stimulatory and inhibitory effects (30). The
early demonstration of increased DNA synthesis in
human hair follicles with minoxidil sulfate also involved
a more basic serum-free medium without supplementation
with insulin or hydrocortisone (38). Insulin was
originally added to the medium to prevent cultured
follicles from entering a catagen-like state (52), i.e., to
prolong anagen, the effect that minoxidil has in vivo.
When follicles were cultured here in insulin- and
hydrocortisone-free medium, control follicles rapidly
entered a catagen-like state (Fig. 5) as reported earlier
(52).
However, the addition of minoxidil (1 mM)
prolonged the anagen period, replicating the effect on
hair follicles when minoxidil is used in vivo in the
clinical situation (8); a smaller amount of minoxidil (10
M) had only a reduced stimulatory effect (Fig. 5).
Tolbutamide had no effect on its own, but blocked
stimulation by minoxidil (1 mM) when they were used
in combination (Fig. 5). Insulin has various effects on
cells, which differ depending on the cell type but
generally include increased uptake of energy-providing
molecules such as glucose and promotion of their
incorporation into storage molecules. In addition, insulin
activates membrane Na,K ATPases, which increase
the movement of sodium ions out of and potassium
ions into the cell. Such changes may cause KATP
channels to open, preventing minoxidil from exerting
any effect on the follicles via the KATP channel mechanism
in the standard medium.
The counteracting of the stimulatory effect of minoxidil
by tolbutamide in insulin-free medium and
prevention by minoxidil of the stimulation by tolbutamide
in medium containing insulin strongly suggest
that both substances are acting via KATP channels in
these situations, rather than by any other route that
may be possible at the high concentrations used. Tolbutamide
has a higher affinity for SUR1 KATP channels
and would block any such channels at this concentration
concentration.
However, tolbutamide also has a lower affinity to
SUR2B channels which, if present, should also be
closed at the concentrations used in these experiments
(53–55). Because
minoxidil only acts via SUR2 channels,
these results suggest actions via SUR2 channels in
organ culture.
Molecular biological and immunohistological
demonstration of two types of KATP channels in
human hair follicles
παιδιά η ερευνα είναι τεράστια... το θέμα είναι και το ερώτημα (κος Κάπα ice και υπόλοιποι αν βρούμε kATP chanell opener για τα SURB κανάλια = ραστα ? )
εδώ
http://molpharm.aspetjournals.org/content/74/5/1333.full.pdf
λέει αυτό
SUR2 channels are sensitive to pinacidil. It
is generally believed that SUR1 and SUR2 are incompatible in
channel coassembly. We used triple tandems, T1 and T2, each
containing one SUR (SUR1 or SUR2A) and two Kir6.226 (last
26 residues are deleted) to examine the coass
μινοξ + pinacidil = rasta ?
SUR1SUR2A channels were sensitive to
azide,
diazoxide,
and
pinacidil, and their single-channel burst duration was 2-fold
longer than that of the T1 channels. Furthermore, SUR2A was
coprecipitated with SUR1. Using whole-cell recording and immunostaining,
