Alpha 1B-adrenoceptor-mediated excitation of piriform cortical interneurons.
Pharmacological techniques have defined the existence of two different alpha 1-adrenoceptors, the alpha 1A- and alpha 1B-adrenoceptor subtypes and both of these receptors have been cloned in addition to a cloned alpha 1d-adrenoceptor. A subpopulation of interneurons in layer III of the rat piriform cortex that are excited by 5-hydroxytryptamine (5-HT) via 5-HT2A receptors are also excited by norepinephrine via alpha 1-adrenoceptors. In the present study we determined the pA2 values against the norepinephrine-mediated excitation of piriform cortical interneurons for a number of antagonists that are (1) not selective for alpha 1A- or alpha 1B-adrenoceptors (prazosin), (2) selective for alpha 1A-adrenoceptors (5-methyl urapidil, 2-(2,6-dimethoxy-phenoxyethyl)- aminomethyl-1,4-benzodioxane hydrochloride (WB 4101), benoxathian, phentolamine) and (3) selective for alpha 1B-adrenoceptors (spiperone and risperidone). The pA2 values for the antagonist blockade of norepinephrine-mediated interneuron excitation were significantly correlated to literature values for the pKi values of antagonist binding to the alpha 1B-adrenoceptor (r = 0.919) and the cloned alpha 1b-adrenoceptor (r = 0.849) but were not correlated to the pKi values of antagonist binding to the alpha 1A-adrenoceptor or the cloned alpha 1a- and alpha 1d-adrenoceptor. Thus, we conclude that this population of piriform cortical interneurons is excited by norepinephrine via alpha 1B-adrenoceptors.
Marek
G J
GJ
Department of Psychiatry, Yale University School of Medicine, Ribicoff Research Facilities of the Connecticut Mental Health Center, New Haven 06508, USA.
Aghajanian
G K
GK
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004146:Dioxanes / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010075:Oxathiins / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D018967:Risperidone / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
C547718:Adra1b protein, rat; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010075:Oxathiins; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D013134:Spiperone; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C050877:benoxathian; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D018967:Risperidone; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine