SUMMARYThis study investigates the effects of magnesium (Mg2+) on acetylcholine (ACh)-evoked secretory responses and calcium (Ca2+) mobilization in the isolated rat pancreas. ACh induced marked dose-dependent increases in total protein output and amylase release from superfused pancreatic segments in zero, normal (1 1 mM) and elevated (10 mM) extracellular Mg24.

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SUMMARY1. A comparative study was made of the effect of the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA) on cholecystokinin octapeptide-evoked exocrine pancreatic secretion in the anaesthetized rat and isolated permeabilized pancreatic acinar cells.2. Cholecystokinin octapeptide (CCK8; 0-10-6-40 nmol (kg body weight)-') induced dose-dependent increases in pancreatic juice flow, total protein output and amylase release in the anaesthetized rat.3. Administration of TPA (10-8 mol (kg body weight)-') in combination with CCK8 resulted in marked attenuation of the CCK8-evoked secretory response.4. Simultaneous injection of polymyxin B (10-8 mol (kg body weight)-'), an inhibitor of protein kinase C, with TPA and CCK8 reversed the inhibitory effect of the phorbol ester on CCK8-induced pancreatic juice flow, total protein output and amylase release.5. In permeabilized rat pancreatic acini CCK8 (10-13-10-9 M) elicited dosedependent increases in [3H]leucine-labelled protein secretion (3H-labelled protein release). Combining TPA (10-8 M) with CCK8 resulted in an inhibition of the CCK8-induced 3H-labelled protein release especially at lower concentrations of CCK8. At higher concentrations of CCK8, TPA was unable to inhibit the CCK8-evoked 3H-labelled protein release. Again, polymyxin B reversed the TPA-induced inhibition of CCK8-evoked 3H-labelled protein output.6. The results indicate that protein kinase C activation may play an important physiological role in modulating the CCK8-evoked secretory response in rat pancreas in vivo and in vitro.

The effects of histamine alone and histamine plus cimetidine on basal pancreatic exocrine secretion were determined in anaesthetized rabbits with an acute pancreatic cannula. Intravenous histamine administration (0.2-0.8 n mol/kg/min) increased pancreatic enzyme secretion. A much greater stimulative effect on pancreatic secretion was observed when histamine was administered against a constant background of H2 antagonist (cimetidine 4 mumol/kg/min). The results indicate that in the rabbit pancreas the stimulatory effect of histamine is mediated by H1 receptors.

SUMMARYThe effects of the phorbol ester, 12-tetradecanoyl-phorbol-13-acetate (TPA) and related compounds on acetylcholine (ACh)-evoked [3H]leucine-labelled protein release (secretion) were tested in isolated permeabilized rat pancreatic acini. The aim was to determine whether the diacylglycerol-like compounds can still potentiate the actions of ACh during unfluctuating supramaximal elevation ofcytosolic free calcium (Ca2+) levels. TPA and R59 022, an inhibitor of diacylglycerol kinase, evoked marked biphasic dose-dependent increases in 3H-labelled protein secretion from permeabilized rat pancreatic acini. Synthetic diacylglycerol (OAG) and 8-bromo cyclic GMP elicited small increases in 3H-labelled protein release while an inactive phorbol ester (4a.-phorbol-12,13-didecanoate; 4a-PDD) and polymyxin B, an inhibitor of protein kinase C, were unable to stimulate secretion. Combining polymyxin B with TPA resulted in an inhibition of 3H-labelled protein secretion. Acetylcholine also induced a dose-dependent increase in 3H-labelled protein output, but when TPA or R59022 was combined with ACh, there was a marked potentiation of the ACh-evoked secretory response, particularly at higher concentrations of ACh. This synergism was unaffected by the protein kinase C inhibitor, polymyxin B. The results show that cytosolic free Ca2+ and protein kinase C may not be the only mediators of ACh-evoked secretion. Moreover, they indicate that protein kinase C may not be involved in the potentiation by TPA of ACh-evoked 3H-labelled protein release.