Alpha(2)-adrenoceptor-stimulated GTP gamma S binding in rat brain: an autoradiographic study.
Agonist-stimulated [35S]GTP gamma S binding by alpha(2)-adrenoceptors was examined in rat brain by autoradiography. Epinephrine, norepinephrine, dexmedetomidine and brimonidine stimulated [35S]GTP gamma S binding in a dose-dependent manner. Agonist-stimulated binding was blocked by the specific alpha(2)-adrenoceptor antagonist (1, 4-benzodioxan-2-methoxy-2-yl)-2-imidazoline hydrochloride (RX821002). Each alpha(2)-adrenoceptor agonist stimulated [35S]GTP gamma S binding in the same brain regions, corresponding to alpha(2)-adrenoceptor distribution determined by [125I]para-iodoclonidine autoradiography. The order of antagonist potency (RX821002>idazoxan>rauwolscine>phentolamine>prazosin), and weak inhibition by propranolol and selective serotonin antagonists, indicate that epinephrine-stimulated [35S]GTP gamma S binding is mediated primarily by alpha(2)-adrenoceptors. Several antagonists increased [35S]GTP gamma S binding at very high concentrations, and this effect had anatomic and pharmacologic characteristics of binding mediated by 5-HT(1A) receptors. These studies demonstrate functional linkage of alpha(2)-adrenoceptors to G proteins in tissue sections, thus providing data on neuroanatomic localization and a means to examine drug specificity at alpha(2)-adrenoceptors in different brain regions.
Happe
H K
HK
Department of Pharmacology, University of Nebraska Medical Center, 986260 Nebraska Medical Center, Omaha, NE 68198-6260, USA.
Bylund
D B
DB
Murrin
L C
LC
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology
D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000068438:Brimonidine Tartrate; C058525:2-methoxyidazoxan; D019329:Idazoxan; D004837:Epinephrine