Output of prostaglandin E2 (PGE2) from guinea pig ileal strips was detected by radioimmunoassay and the effect of adenosine and adenosine nucleotides on PGE2 output investigated in vitro. Adenosine triphosphate (ATP) and alpha, beta-methylene ATP, as well as adenosine, stimulate the output of PGE2 in a concentration dependent-manner. Potency of these compounds is in the order of alpha, beta-methylene ATP greater than ATP greater than adenosine. The effect of ATP was totally blocked by the cyclooxygenase inhibitor, indomethacin. Actions of these adenylyl compounds were attenuated by apamin, an antagonist of postjunctional P2-purinoceptor-mediated activity. Effectiveness of these compounds was not modified by 8-phenyltheophylline, a P1-purinoceptor antagonist, and it was not obtained in the isolated synaptosomal preparations. In addition, effects of adenosine and adenosine nucleotides were augmented only slightly by dipyridamole, a blocker of adenosine uptake. These findings suggest that the formation of PGE2 is stimulated in muscle cells, through the postjunctional P2-purinoceptor, taking an active role in the purinergic neurotransmission of guinea pig gut.
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