Lm. Kow et Dw. Pfaff, FUNCTIONAL ANALYSES OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN RAT HYPOTHALAMIC VENTROMEDIAL NUCLEUS NEURONS, European journal of pharmacology, 282(1-3), 1995, pp. 199-206
Activation of alpha(1)-adrenoceptors in rat hypothalamic ventromedial
nucleus can excite neurons and facilitate female sexual behavior. To i
dentify the alpha(1)-adrenoceptor subtype(s) involved, the alpha(1B)-a
drenoceptor-specific antagonist chloroethylclonidine (100 mu M) and/or
the alpha(1A)-adrenoceptor-selective antagonist 5-methyl urapidil (1
or 2.5 mu M) or WB-4101 (0.1-10 mu M) were applied to a recording cham
ber bathing the hypothalamic slice containing the ventromedial nucleus
. In all the neurons tested, both types of antagonists blocked, often
completely, excitatory responses to nonselective alpha(1)-adrenoceptor
agonists. Since the doses used were unlikely to make these antagonist
s nonselective, the results suggest that activation of both alpha(1A)-
and alpha(1B)-adrenoceptor subtypes was necessary for alpha(1)-adreno
ceptor agonists to evoke an excitation, or that with the present appli
cation method - injection into the continuously perfused chamber - chl
oroethylclonidine did not act specifically. In preincubation (at 37 de
grees C for 90 min) where it was reported to act by specific alkylatio
n, chloroethylclonidine (100 mu M) but not the vehicle abolished the e
xcitation evoked by an alpha(1)-adrenoceptor agonist, but not that by
carbachol or other excitants. Also, either in bath application or incu
bation, chloroethylclonidine worked equally efficiently on slices from
ovariectomized rats, that reportedly contain few alpha(1)-adrenocepto
rs, and from those treated with estrogen which induces alpha(1B)-adren
oceptors selectively, suggesting that alpha(1B)-adrenoceptor was neces
sary even when in low abundance. Thus, it is likely that the activatio
n of both alpha(1A)- and alpha(1B)-adrenoceptor subtypes and also ther
eby, their respective couplings to second messengers are necessary to
mediate the actions of alpha(1)-adrenoceptor agonists in exciting hypo
thalamic neurons.