Stimulation of inositol trisphosphate accumulation and amylase secretion by caerulein in pancreatic acini.
Inositol trisphosphate (IP3), formed by receptor-mediated breakdown of triphosphoinositide, may function as the messenger to mobilize Ca++ in certain cells. The effects of the peptidergic agonist caerulein on the formation of IP3 and amylase secretion in rat pancreatic acini prelabeled with [3H]inositol have therefore been compared. Caerulein elicited rapid increases in [3H]IP3, which subsequently declined after 2 min. Inositol bisphosphate and inositol phosphate, which are produced by the degradative action of phosphatase on IP3, were also increased. Lithium enhanced the action of caerulein on the accumulation of inositol phosphates at later time periods (5-30 min), but failed to augment the secretory response to caerulein. In the presence of lithium, the time course and the concentration-response curves of caerulein-stimulated IP3 accumulation and amylase secretion increased in a parallel fashion; however, IP3 accumulation continued to increase with higher caerulein concentrations than those which elicited maximal enzyme secretion. These findings fortify the concept that peptidergic receptor agonists, like muscarinic agonists, express their effects on the secretory process of the exocrine pancreas through the formation of IP3 derived from the hydrolysis of triphosphoinositide. The mechanism of this event seems to involve spare receptors.
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002108:Ceruletide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*; D013997:Time Factors
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D002108:Ceruletide; D008094:Lithium; D000681:Amylases; D002118:Calcium