Abstract
THE pancreatic acinar cell discharges secretory proteins in response to cholecystokinin–pancreozymin (CCK–PZ) and its analogues, or to cholinergic agonists such as carbamylcholine (carbachol). The mechanisms for stimulus–secretion coupling in the acinar cell are not known, although intracellular and, to some extent, extracellular Ca2+ are required1–4, and a transient 10- to 20-fold increase in intracellular levels of guanosine cyclic 3′5′-monophosphate (cyclic GMP) accompanies onset of induced discharge5,6. It has been proposed5 that cyclic GMP may be a direct mediator of hormone-stimulated discharge, with the Ca2+-dependent event either causing, or being caused by, increases in cyclic GMP7,8. To test this hypothesis, we have monitored the effects of several substances on secretory protein discharge and intracellular cyclic GMP levels in guinea pig pancreatic acini. Our results, reported here, are not consistent with a role for cyclic GMP in a direct causative pathway leading to discharge, as four of the compounds tested (N-methyl-N-nitro-N-nitrosoguanidine (MNNG), sodium nitrite, hydroxyl-amine and sodium nitroprusside) elevated levels of cyclic GMP but did not trigger discharge, although acini treated with these agents remained competent to respond to natural secretagogues. Conversely, the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) did not affect cyclic GMP levels, but did elicit discharge. In contrast to observations on cyclic GMP, the requirement for extracellular Ca2+ correlated well with discharge. Our findings therefore do not support the hypothesis that cyclic GMP is directly involved in stimulus–secretion coupling, but are consistent with such a role for Ca2+. A preliminary report of this work has appeared9.
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GUNTHER, G., JAMIESON, J. Increased intracellular cyclic GMP does not correlate with protein discharge from pancreatic acinar cells. Nature 280, 318–320 (1979). https://doi.org/10.1038/280318a0
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DOI: https://doi.org/10.1038/280318a0
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