The effects of gastrin and gastrin analogues on pancreatic acinar cell membrane potential and resistance

Intracellular recordings of membrane potentials and input resistance have been made from the exocrine acinar cells of mouse and rat pancreas placed in a tissue bath perfused with Krebs-Henseleit solution. The resting acinar cell membrane potential was about -38 mV. The acinar cells were stimulated by cholecystokinin-pancreozymin (CCK-PZ), gastrin and the gastrin-related polypeptides, caerulein and desulphated caerulein. The immediate effect of stimulation with these secretagogues was always a depolarization and a concomitant reduction in input resistance and time constant. Depolarization of the acinar cell membrane by these secretagogues was not abolished in the presence of atropine (1.4 μM). These peptide secretagogues were divided into the gastrin group and the CCK-PZ group according to the time course of the depolarizations and the shape of the dose-response curve. The depolarization evoked by the gastrin group returned quickly to the resting level but that evoked by the CCK-PZ group was long lasting. The time course and the dose-response curve for desulphated caerulein was identical with that of gastrin. It was confirmed electrophysiologically that the activity of gastrin is exerted by the C-terminal tetrapeptide: but the activity of caerulein depends on the C-terminal heptapeptide, especially the presence in the molecule of the sulphated tyrosyl residue at position 7 (numbering from the C-terminus). The equivalent sulphated tyrosyl residue in CCK-PZ is probably necessary for optimal activity of this polypeptide. The dose-response curves obtained by electrophysiological methods indicated that the relative potencies of the peptides on mouse pancreatic acinar cells were caerulein > CCK-PZ > gastrin. Synthetic human gastrin I was found to have a higher potency than either tetragastrin or pentagastrin.