B-HT 920 acts as an alpha 1-adrenoceptor agonist in the rabbit aorta under certain in vitro conditions.
We have investigated the interaction of the alpha 2-adrenoceptor agonist B-HT 920 with the alpha-adrenoceptors in the rabbit aorta using various experimental conditions. In standard Krebs-Henseleit solution B-HT 920 behaved as an antagonist when tested against the alpha 1-agonist phenylephrine. However, it behaved as a partial agonist at alpha-receptors when subcontractile concentrations of various spasmogens (angiotensin II, serotonin, prostaglandin F2 alpha) were applied, although no change in the affinity of the receptor to B-HT 920 was observed. By means of the selective antagonists prazosin and rauwolscine it was established that B-HT 920 activated alpha 1-receptors. The same agonistic effects of B-HT 920 were obtained after pretreatment of the animal with reserpine or in the presence of ouabain. The various treatments used (except reserpine) did not influence the contractile response to phenylephrine. The contractile response to B-HT 920 was found to be highly susceptible to the calcium entry blocker nitrendipine whereas the response to phenylephrine was not. It is concluded that spasmogens modulate the responsiveness of alpha-receptors to certain agonists, possibly by causing a depolarization of the cell membrane and, thereby, sensitization of a mechanism involved in excitation-contraction coupling, conceivably a calcium gating mechanism.
D000316:Adrenergic alpha-Agonists; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D007473:Ion Channels; D000804:Angiotensin II; D010656:Phenylephrine; D015016:Yohimbine; C024763:talipexole; D012110:Reserpine; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium