title: Alpha 1-adrenoceptors of rat myocardium: comparison of agonist binding and positive inotropic response.
abstract: Binding of agonists to alpha 1-adrenoceptors labelled by 3H-prazosin was investigated in membranes of rat myocardium and compared to the inotropic response elicited by alpha 1-adrenoceptor activation on isolated right ventricles. 1. At 30 degrees C the full agonists, adrenaline and phenylephrine, displaced 3H-prazosin with a shallow inhibition curve. The data are compatible with the assumption that 32% of the binding sites were in a state of high affinity for the agonist adrenaline (KI 85 nmol/l) and 68% in a low affinity state (KI 1738 nmol/l). GTP transformed all binding sites into the low affinity form suggesting that at least some of the cardiac alpha 1-adrenoceptors are coupled to N-proteins. 2. At 0 degree C most of the binding sites (86%) were in a state of high affinity for agonists (KI for adrenaline: 91 nmol/l). 3. For several partial agonists and antagonists (cirazoline, methoxamine, indanidine (Sgd 101-75), oxymetazoline and phentolamine) no such distinct temperature- and GTP-shifts could be demonstrated suggesting a different kind of interaction with alpha 1-binding sites. 4. When temperature was changed during incubation with adrenaline, a rise of temperature (from 0 degrees C to 30 degrees C) converted high affinity sites into the low affinity form, whereas a decrease in temperature (from 30 degrees C to 0 degrees C) failed to induce the high affinity state for agonists. Short term incubation (0.5 min) with adrenaline at 30 degrees C resulted in significantly lower IC50 values as compared to equilibrium conditions at the same temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Pharmakologisches Institut des Universitätsklinikums Essen, Federal Republic of Germany.
authors.forename: G
authors.initials: G
authors.lastname: Gross
authors.forename: G
authors.initials: G
authors.lastname: Hanft
authors.forename: C U
authors.initials: CU
authors.lastname: Rugevics
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013696:Temperature
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D012110:Reserpine; D011224:Prazosin