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Abstract

Inhibition of guinea-pig oxyntic cell function by adenosine and prostaglandins.

A A Heldsinger, A I Vinik and I H Fox
Journal of Pharmacology and Experimental Therapeutics May 1986, 237 (2) 351-356;
A A Heldsinger
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A I Vinik
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I H Fox
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Abstract

Adenosine and prostaglandins (PGs) are known inhibitors of oxyntic cell function. Using quantitative cytochemistry of hydroxyl ion production (HIP) in guinea-pig oxyntic cells, we examined the effects of adenosine and PGs on secretagogue-stimulated HIP. Adenosine (10(-6) M) inhibited the actions of histamine (10(-14) M) and gastrin (2.5 X 10(-12) M) by 69 and 67%, respectively, but not that of dibutyryl cyclic AMP (10(-16) M) or carbachol (10(-9) M). These observations suggest that adenosine does not influence the Ca++-dependent pathway of carbachol action and that the adenosine activity precedes the generation of cyclic AMP. Adenosine and related analogs, N6-L-phenylisopropyladenosine and 5-N-ethylcarboxam-idoadenosine (10(-12) to 10(-14) M), inhibited histamine-stimulated HIP (10(-14) M) in the following order: N6-L-phenylisopropyladenosine greater than 5-N-ethylcarboxamidoadenosine greater than adenosin. The adenosine antagonist, 1,3-diethylphenylxanthine (10(-6) M), reversed the inhibitory effects of adenosine. Exogenous PGE2 (10(-6) M) also inhibited histamine- and gastrin-stimulated HIP by 65 and 55%, respectively. Indomethacin (10(-6) M) and flurbiprofen (10(-6) M), PG synthesis inhibitors, potentiated the action of histamine by 175 and 159%, respectively. Adenosine was incapable of reversing this potentiated effect. These data indicate that adenosine and related analogs are inhibitors of oxyntic cell HIP and suggest that these biological properties are mediated by binding to a cell surface receptor and thereby regulating oxyntic cell adenylate cyclase activity. The more potent properties of N6-L-phenylisopropyladenosine as compared to 5-N-ethylcarboxamidoadenosine are consistent with activity at the high-affinity surface adenosine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 237, Issue 2
1 May 1986
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Abstract

Inhibition of guinea-pig oxyntic cell function by adenosine and prostaglandins.

A A Heldsinger, A I Vinik and I H Fox
Journal of Pharmacology and Experimental Therapeutics May 1, 1986, 237 (2) 351-356;

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Abstract

Inhibition of guinea-pig oxyntic cell function by adenosine and prostaglandins.

A A Heldsinger, A I Vinik and I H Fox
Journal of Pharmacology and Experimental Therapeutics May 1, 1986, 237 (2) 351-356;
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