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Molecular Pharmacology, Vol 12, 49-58, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Adenosine Cyclic 3',5'-Monophosphate in the Liver Fluke, Fasciola hepatica

I. Activation of Adenylate Cyclase by 5-Hydroxytryptamine

SANDERS L. ABRAHAMS 1, JOHN K. NORTHUP 1, and TAG E. MANSOUR 1

1 Department of Pharmacology, Stanford University School of Medicine, Stanford, California 94305

5-Hydroxytryptamine caused a marked accumulation of endogenous adenosine cyclic 3',5'-monophosphate in the liver fluke, Fasciola hepatica, especially in the anterior end ("head") of the organism. The accumulation of the cyclic nucleotide and the accompanying increase in motility of the isolated fluke head were dependent on 5-hydroxytryptamine concentration. Adenylate cyclase in particles from fluke heads also showed a greater activation by 5-hydroxytryptamine than did particles from the posterior end of the fluke. The ability of indoleamine analogues of 5-hydroxytryptamine to stimulate fluke motility and to activate adenylate cyclase was found to diminish with decreasing structural similarity of the analogue to 5-hydroxytryptamine. Both the free amino and 5-hydroxyl groups of 5-hydroxytryptamine appear to be important for its recognition by adenylate cyclase. The results support the hypothesis that adenosine cyclic 3',5'-monophosphate acts as a second messenger for 5-hydroxytryptamine in invertebrates. On the other hand, this investigation suggests no direct relationship between the elevation of the cyclic nucleotide and the stimulation of motility. Both amphetamine and D-lysergic acid diethylamide stimulated fluke motility but did not cause an increase in endogenous levels of the cyclic nucleotide. Moreover, D-lysergic acid diethylamide antagonized the 5-hydroxytryptamine activation of adenylate cyclase. The results suggest that this antagonism may be related to the high affinity of D-lysergic acid diethylamide for its site on adenylate cyclase.

Submitted on July 7, 1975




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