Neurohormonal and Hormonal Control of Pancreatic Secretion

The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas

“…With regard to CCK, we know the physiological levels in the plasma, which, as already mentioned, are in the range of 1 -10 pM (192) and it has been repeatedly shown that such very low levels of CCK induce opening of Ca 2+activated Clchannels and directly measured [Ca 2+ ] i elevations in the acinar cells (215,231,282) including, as already described in the previous section, in the human pancreas (152,182). Taken all this together, there is a strong case for concluding that Ca 2+ signals in pancreatic acinar cells play a critical role in physiological control of enzyme secretion in the intact body.…”

“…Although the studies of CCK action on isolated pancreatic acinar cells, as well as on acinar cells in the more intact lobule or slice preparations, would appear to provide evidence indicating that CCK stimulates pancreatic enzyme and fluid secretion by directly activating CCK1 receptors on the acinar plasma membrane, this is not a view universally shared (215). Even in the rat, where it is undisputed that CCK can act directly on isolated acinar cells to generate Ca 2+ signals and secretion, it has been proposed that this action is not physiologically relevant and that the effect of CCK in vivo is mediated via cholinergic nerves.…”

“…There is also a question about the physiological levels of stimulation. There are no data about the ACh concentrations attained near the muscarinic receptor sites during low frequency (physiological) nerve stimulation, but we do know the physiological concentration range of CCK (1-10 pM) (174,215,277). At these low concentrations, the latency for activation of the Ca 2+ -dependent Clcurrent is very variable and can be very long (minutes) (243).…”

“…It is undisputed that, in all these species, CCK -in all its active forms, CCK8, CCK33, CCK58 -acts on specific high-affinity receptors (CCK1 receptors) on pancreatic acinar cells (63,139). However, there has been, and to some extent still is, a dispute about the existence of functional CCK receptors on human pancreatic acinar cells and therefore whether the undisputed fact that CCK stimulates pancreatic enzyme secretion in vivo is due to direct action of CCK on acinar cells or is indirect via stimulation of vagal nerves (215).…”

“…Even in the rat, where it is undisputed that CCK can act directly on isolated acinar cells to generate Ca 2+ signals and secretion, it has been proposed that this action is not physiologically relevant and that the effect of CCK in vivo is mediated via cholinergic nerves. The opposing views are clearly articulated in the most recent (3 rd ) edition of 'The Pancreas' in the chapters by Petersen (247) and Owyang (215). The principal argument in favour of the hypothesis that the CCK action on the pancreas is indirect, rests on important in vivo experiments conducted by Li & Owyang (172).…”