Functional analyses of alpha 1-adrenoceptor subtypes in rat hypothalamic ventromedial nucleus neurons.
Activation of alpha 1-adrenoceptors in rat hypothalamic ventromedial nucleus can excite neurons and facilitate female sexual behavior. To identify the alpha 1-adrenoceptor subtype(s) involved, the alpha 1B-adrenoceptor-specific antagonist chloroethylclonidine (100 microM) and/or the alpha 1A-adrenoceptor-selective antagonist 5-methyl urapidil (1 or 2.5 microM) or WB-4101 (0.1-10 microM) were applied to a recording chamber 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 antagonists nonselective, the results suggest that activation of both alpha 1A- and alpha 1B-adrenoceptor subtypes was necessary for alpha 1-adrenoceptor agonists to evoke an excitation, or that with the present application method--injection into the continuously perfused chamber--chloroethylclonidine did not act specifically. In preincubation (at 37 degrees C for 90 min) where it was reported to act by specific alkylation, chloroethylclonidine (100 microM) but not the vehicle abolished the excitation evoked by an alpha 1-adrenoceptor agonist, but not that by carbachol or other excitants. Also, either in bath application or incubation, chloroethylclonidine worked equally efficiently on slices from ovariectomized rats, that reportedly contain few alpha 1B-adrenoceptors, and from those treated with estrogen which induces alpha 1B-adrenoceptors selectively, suggesting that alpha 1B-adrenoceptor was necessary even when in low abundance.(ABSTRACT TRUNCATED AT 250 WORDS)
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D007033:Hypothalamus, Middle / Q000737:chemistry* / Q000166:cytology; D066298:In Vitro Techniques; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D010656:Phenylephrine; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine