title: Alpha 1-adrenergic receptors in neuronal cultures from rat brain: increased expression in the spontaneously hypertensive rat.
abstract: Neuronal cells in primary culture from 1-day-old brains of normotensive, Wistar-Kyoto strain (WKY) and spontaneously hypertensive (SH) rats have been utilized to study the expression of alpha 1-adrenergic receptors. Binding of a selective alpha 1 antagonist, [125I]2-[beta-(4-hydroxy-3-iodophenyl)-ethylaminomethyl]-tetralone ([125I]HEAT) to neuronal membranes prepared from primary brain cultures of WKY and SH rats was 75-80% specific, rapid, and time-dependent although the binding was 1.5-2 times higher in neuronal membranes from SH rat brain cultures. Kinetic analysis of the association and dissociation data demonstrated no significant differences between rat strains. Competition-inhibition experiments provided IC50 values for various antagonists and agonists in the following order: prazosin less than phentolamine less than yohimbine less than phenylephrine less than norepinephrine less than propranolol, suggesting that [125I]HEAT bound selectively to alpha 1-adrenergic receptors. Scatchard analysis of the binding data provided straight lines for both strains of rats, indicating the presence of a homogeneous population of binding sites. It also showed that the increase in the binding in neuronal cells from SH rat brains over those from normotensive WKY controls was a result of an increase in the number of alpha 1-adrenergic receptors. Incubation of neuronal cultures from both strains of rats with phenylephrine, an alpha 1-adrenergic agonist, caused a time- and dose-dependent decrease in the binding of [125I]HEAT. This decrease was due to a decrease in the number of alpha 1-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000166:cytology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism*; D007700:Kinetics; D009474:Neurons / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D044024:Tetralones
chemical_list: D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; D010656:Phenylephrine; C048008:2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone