Stimulation of pancreatic secretion by non-sulfated CCK-58 gives insight into neurohormonal regulation of the pancreas

Abstract

Non-sulfated cbolecystcMmn-58 (CCK-58ns) has been shown to be present m porcine and canine intestine, This form ot cholecystokinin may have been ignored by our laboratory in previous studies because it reacts very poorly in our radioimmunoassay with antibody 5135 (about 10% as potent as CCK-8s. However, it is present in the intestine at about half the concentration of CCK-58s. A maior bi-product from the synthesis and purification of rat CCK-58s is CCK-58ns. Syrabenc CCK-58ns was wall separated from CCK-58s, and was used to stinmlate pancreatic secretion in awake rats. CCK-58ns was as potent and one-half as effacions as CCK.-58s for stimulation ot pancreatic find and protein. CCK-8s was as potent as the CCK-58 peptides for stimulation of prutem, but CCK-8 did not stimulate fluid secretion (Figure). A model that would account tbr these results is one where both the acmar CCK-A receptor and the CCK-A receptor on intrapancreatic nerves regulate pancreatic secretion. The nanral CCK-A receptor is mediated by a neumtransmttter that can be blocked by atropine and it stinmlates both protein and fuid. We propose that this neural receptor is not activated by CCK-8s at any concetrations, possibly because CCK-8s is inactivated by neural endopeptidease before it reaches the neural CCK-A receptor. This is supported by the tact that CCK-58s is resistant to this endopepfidase degradation while CCK-8s is rapidly cleaved. We barther propose that the CCK-A receptor m~ aciuar cells is not activated by CCK-58ns and its inability to react with this receptor causes the decreased efficacy compared to CCK-58s. In conclusion, CCK-58ns is present in intestine and it has a unique pattern for stimulating pancreanc secretion that leads to new hypotheses about regulation of pancreatic secretion.