title: Inhibition of alpha 1-adrenergic responsiveness in intact cells by a new, irreversible receptor antagonist.
abstract: A novel alpha 1-adrenoreceptor antagonist, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo [2.2.2] octa-2,5-dienylcarbonyl) piperazine, was synthesized and shown to potently block alpha 1-adrenoceptor-induced Ca2+ mobilization in intact rat parotid acinar cells. Irreversible inhibition was complete in less than 5 min. This alkylating prazosin derivative blocked Ca2+ release (IC50 approximately 5 X 10(-10)M) and [3H]-prazosin membrane binding (IC50 approximately 3 X 10(-10)M) in a concentration dependent fashion and increased the EC50 of epinephrine for Ca2+ efflux by approximately 35 fold. The agent however had no effect on muscarinic receptor-induced Ca2+ mobilization, or beta-adrenoreceptor-induced protein secretion, from cells. These findings suggest that this irreversible alpha 1-adrenoreceptor antagonist will be a valuable tool in probing alpha 1-adrenoreceptor function and metabolism in intact cells.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; C051307:SZL 49; D002118:Calcium; D011224:Prazosin; D004837:Epinephrine