Alpha-1 adrenergic coupling events induced by full and partial agonists in rabbit aorta.
Differences in the ability of full vs. partial agonists to initiate alpha-1 adrenergic receptor-mediated coupling events were studied in isolated segments of rabbit aorta. Mono- and dimethoxysubstituted tolazolines produced contractile responses which, at their maximum, were 27 to 100% of the response produced by the full agonist phenylephrine. In addition to differences in maximum response, contraction kinetics varied between full and partial agonists. Responses to partial agonists displayed a slower approach to peak tension and loss of the rapid phase of tension development which is associated with release of intracellular Ca++. Among the tolazoline series 3,5 dimethoxy-, 3 methoxy-, and 2 methoxy derivatives were compared further with phenylephrine for their ability to cause phosphatidylinositol cycle turnover, intracellular Ca++ release and Ca++ influx. For each of these coupling events, a rank of phenylephrine greater than or equal to 3, 5 greater than 3 greater than 2 was observed. However, a higher percentage of Ca++ influx vs. Ca++ release was observed for the partial agonists, suggesting that their contractile responses may be more dependent upon extracellular Ca++ than intracellular Ca++. Our results indicate that partial agonists initiate the same coupling events as full agonists; however, the relative proportion of Ca++ release and influx may be different for partial agonists because of the reduced rate of second messenger production.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014043:Tolazoline / Q000031:analogs & derivatives / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D007811:Lanthanum; D014043:Tolazoline; D002118:Calcium