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Inhibition of histamine-sensitive adenylate cyclase from guinea pig fundic gastric mucosa by arachidonic acid and by an analog of prostaglandin endoperoxide PGH2

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Abstract

The effects of prostaglandin precursors, namely an analog of prostaglandin endoperoxide PGH2 [(15S)-hydroxy-9α,11α-(epoxymethano)prosta-5, 13-dienoic acid] and arachidonic acid, were assessed on gastric adenylate cyclase activity from cell-free preparations of guinea pig fundic mucosa. The two precursors were tested against basal adenylate cyclase activity and that stimulated by histamine (10−4M), by PGE2(10−4M), by 5′-guanylylimidodiphosphate [Gpp(NH)p] (10−4M) and by NaF(10−2M). PGH2 analog (10−4M) and arachidonic acid (10−4M) both inhibited to a similar extent adenylate cyclase stimulated by histamine or by NaF, but not that stimulated by PGE2 or by Gpp(NH)p. Neither agent significantly affected basal adenylate cyclase levels. In the presence of indomethacin (10−4M), basal adenylate cyclase activity remained unchanged but the inhibitory effect of arachidonic acid was almost entirely abolished, suggesting that such inhibitory effect may be caused by prostaglandin endoperoxides generated from arachidonic acid in the course of assay. Moreover, indomethacin did not attenuate PGH2 inhibition of histamine action. Unlike arachidonic acid, which is a natural metabolic precursor of PGE2, arachidic acid did not significantly influence histamine-stimulated adenylate cyclase activity. These results suggest that the prostaglandin endoperoxides may have an inhibitory effect on histamine-sensitive ciclic AMP generation in gastric mucosa.

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Authors and Affiliations

  1. Departments of Surgery, Medicine and Physiology Mayo Clinic and Mayo Foundation, 55901, Rochester, MN

    Roger R. Dozois MD, Thomas H. Madson BA & Thomas P. Dousa MD, PhD

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  1. Roger R. Dozois MD
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  2. Thomas H. Madson BA
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  3. Thomas P. Dousa MD, PhD
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This research was supported by NIH grant AM16105, by Biomedical Research Support grant 5 S01 RR 05530-14, and by the Mayo Foundation.

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Dozois, R.R., Madson, T.H. & Dousa, T.P. Inhibition of histamine-sensitive adenylate cyclase from guinea pig fundic gastric mucosa by arachidonic acid and by an analog of prostaglandin endoperoxide PGH2 . Digest Dis Sci 25, 273–278 (1980). https://doi.org/10.1007/BF01308517

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  • DOI: https://doi.org/10.1007/BF01308517

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