RT Journal Article
SR Electronic
T1 Alpha-1 adrenergic coupling events induced by full and partial agonists in rabbit aorta.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 458
OP 464
VO 241
IS 2
A1 Wick, P F
A1 Keung, A C
A1 Bowler, J J
A1 Deth, R C
YR 1987
UL http://jpet.aspetjournals.org/content/241/2/458.abstract
AB 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.