Interaction of phenoxybenzamine with muscarinic receptors and calcium channels.
Phenoxybenzamine (POB, 10(-6) - 10(-4) M) inhibited the responses of guinea pig ileal longitudinal smooth muscle to both muscarinic agonists and K+-depolarization but was more effective against the agonist-induced responses. POB inhibited binding of both the muscarinic antagonist [3H]quinuclidinyl benzilate (QNB) and the Ca2+ channel antagonist [3H]nitrendipine and was, paralleling its effects on mechanical responses, more effective against [3H]QNB binding. POB reduced specific [3H]QNB binding by a reduction in Bmax with no change in KD, but inhibited [3H]nitrendipine binding by reducing KD with no effect on Bmax. It is suggested that the activity of POB against Ca2+ channels may underlie the ability of POB, and other 2-halogenoethylamines, to inhibit a wide variety of apparently discrete pharmacological events.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014316:Tritium
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011976:Receptors, Muscarinic; D010643:Phenoxybenzamine; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D009568:Nitrendipine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium