Kazuhiko Iwatsuki

Effects of dopamine on exocrine secretion and cyclic nucleotide concentration in the dog pancreas

The effects of intravenous injection of dopamine on pancreatic exocrine secretion and on pancreatic cyclic AMP and cyclic GMP concentrations of mongrel dogs were compared with the effects of secretin and pancreozymin. Dopamine (1--10 micrograms/kg), secretin (0.03--0.3 units/kg) and pancreozymin (0.1--1 units/kg) increased exocrine secretion dose dependently, Sulpiride (0.3--1 mg/kg) and yohimbine (0.3--1 mg/kg), D2-receptor antagonists, inhibited the dopamine-induced exocrine secretion dose-dependently but did not inhibit the secretin- or pancreozymin-induced secretion. Secretin (0.3 units/kg) increased cyclic AMp concentration by about 50% but did not affect cyclic GMP concentration. Pancreozymin (1 unit/kg) slightly increased cyclic AMp concentration but markedly increased cyclic GMP concentration by about 50%. However, dopamine (10 micrograms/kg) increased neither cyclic AMP nor cyclic GMP concentration. These results suggest that dopamine causes exocrine secretion from the dog pancreas through D2-receptors which are not linked to adenylate cyclase.

Effects of nitroprusside on pancreatic juice secretion in the blood-perfused canine pancreas

The effects of nitroprusside on the secretion of pancreatic juice were investigated in preparations of isolated and blood-perfused canine pancreas. Nitroprusside (10-30 micrograms/kg) injected intravenously elicited a dose-dependent increase in pancreatic secretion accompanied by a decrease in blood pressure. Intra-arterial administration of nitroprusside (3-300 micrograms) into the perfused pancreas also elicited an increased secretion in preparations of both constant pressure and constant flow perfusion system. The results suggest that nitroprusside-induced pancreatic secretion may not result from the peripheral vasodilatation caused by nitroprusside. The effect of 100 micrograms of intra-arterial nitroprusside corresponded roughly to that of 0.1 units of secretin or 0.3 units of pancreozymin. Nitroprusside-induced secretion was inhibited by the infusion of ethacrynic acid (1 mg/min), but was not modified by phentolamine, propranolol, atropine, haloperidol, tetrodotoxin and metiamide. Nitroprusside produced a dose-dependent increase in the bicarbonate and protein concentrations in the juice, but had little effect on chloride concentration. This action was different from that of secretin or pancreozymin. It is concluded that nitroprusside may produce an increase in pancreatic secretion by acting directly on pancreatic cells, and that this action may be mediated at least in part through the increase of intracellular cyclic GMP concentration.

Effects of substance P on pancreatic exocrine secretion stimulated by secretin, dopamine and cholecystokinin in dogs

1. The effect of substance P (SP) on pancreatic exocrine responses to exogenous cholecystokinin, secretin, and dopamine, were studied in the isolated and blood‐perfused pancreas of dogs.

Effects of three purine-related compounds on pancreatic exocrine secretion in the dog

1. The effects of adenosine, adenosine 5′‐triphosphate (ATP) and inosine on pancreatic exocrine secretion were investigated in the vascularly isolated and self‐hacmoperfused dog pancreas. Drugs were injected close‐arterially (i.a.) in a single bolus.

Dual actions of glucagon: direct stimulation and indirect inhibition of dog pancreatic secretion

The secretory actions of glucagon on the exocrine pancreas were examined using two kinds of canine preparations. In the isolated and blood-perfused dog pancreas with venous drainage, i.a. injection of glucagon did not inhibit secretin/cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic secretion, but instead dose dependently enhanced both basal and stimulated pancreatic secretion. Glucagon-induced increase of pancreatic secretion was potentiated by 3-isobutyl-1-methylxanthine. In contrast, i.v. bolus injection of glucagon (3 and 10 nmol/kg) first augmented transiently then suppressed secretin/CCK-8-stimulated pancreatic secretion while simultaneously increasing circulating plasma somatostatin immunoreactivity from 14.2 to 214 fmol/ml in anesthetized intact dogs. The inhibition of secretin/CCK-8-stimulated pancreatic secretion and elevation of plasma somatostatin immunoreactivity induced by glucagon were comparable with those due to somatostatin-14. Thus, these results indicate that glucagon stimulates pancreatic secretion directly; the inhibitory action of glucagon is indirect and appears to be related to a rise in the circulating level of somatostatin immunoreactivity.

Effects of the cyclic nucleotide phosphodiesterase inhibitors, rolipram, 3-isobutyl-1-methylxanthine, amrinone and zaprinast, on pancreatic exocrine secretion in dogs.

The effects of the cyclic phosphodiesterase (PDE) inhibitors, rolipram, 3-isobutyl-1-methylxanthine (IBMX), amrinone and zaprinast on pancreatic exocrine secretion were investigated in anesthetized dogs. Rolipram (1-30 nmol), IBMX (44-440 nmol) or zaprinast (1-10 mumol) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but amrinone (up to 53 mumol) did not. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by rolipram and IBMX, but neither was affected by zaprinast. Rolipram elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with rolipram were additive. Rolipram and IBMX, but not zaprinast, increased cyclic AMP concentration but did not affect cyclic GMP concentration. These results suggest that rolipram, IBMX and zaprinast have direct secretory properties on pancreatic exocrine glands of the dog, which may be mediated through the increase of intracellular cyclic AMP concentration, by inhibiting PDE activity. Furthermore, the pancreatic PDE enzyme in the dog pancreas may be mainly a type IV.

Effects of human atrial natriuretic polypeptide on pancreatic exocrine secretion in the dog.

We examined the effects of atrial natriuretic polypeptide (hANP) on exocrine function in the isolated and blood-perfused dog pancreas in situ. Intra-arterial injection of hANP (1-10 micrograms) resulted in the dose-dependent increases of the pancreatic juice secretion. The secretory activity of 3 micrograms of hANP was approximately equal to one third of the secretory activity of 0.1 units of secretin. The use of hANP increased the concentration of bicarbonate but not that of sodium and protein in the pancreatic juice as compared with the basal values. These secretory responses to hANP were not inhibited by treatment with haloperidol, sulpiride, phentolamine, propranolol, atropine, cimetidine or ethacrynic acid. These results suggest that hANP acts directly on the pancreatic exocrine gland to stimulate pancreatic secretion; without, however, increasing sodium excretion. The mechanism of this effect remains to be elucidated.

Effects of YM435, a novel dopamine D1 receptor agonist, on pancreatic exocrine secretion in anesthetized dogs

The effects of YM435, a novel dopamine (DA) D1 receptor agonist, on pancreatic exocrine secretion were investigated in anesthetized dogs. Each drug was injected i.a. as a single bolus. Graded doses of YM435 (0.3-30 nmol) produced dose-dependent increases in the rate of secretion of pancreatic juice, with a maximum effect at approximately 10 nmol, and with a high concentration of bicarbonate and low concentration of protein. SCH23390 (3-30 nmol), a selective D1 receptor antagonist, caused a progressive parallel shift to the right of the dose-response curve for YM435-stimulated pancreatic secretion without changing the maximum response. Schild analysis of the data indicated that the inhibitory constant (Ki) value was 2.9 nmol, and that SCH23390 inhibited YM435-stimulated pancreatic secretion in a competitive manner. Both DA (0.01-3 mumol) and SKF38393 (0.3-30 mumol), a selective D1 receptor agonist, also increased the secretory rate and bicarbonate concentration, and decreased the protein concentration to the same extent as YM435. These results suggest that YM435 is a potent stimulant of pancreatic exocrine secretion by acting on DA D1 receptors of the pancreas in dogs.

Effects of nitroprusside on pancreatic exocrine secretion and cyclic nucleotide concentration in the dog pancreas

The effects of intravenous injection of nitroprusside on pancreatic exocrine secretion and on pancreatic cyclic AMP and cyclic GMP concentrations of mongrel dogs were investigated. Nitroprusside (10-100 micrograms/kg) increased the exocrine secretion together with the increase in cyclic GMP concentration dose dependently but did not affect the cyclic AMP concentration. These results suggest that nitroprusside causes exocrine secretion from the dog pancreas mediated through an increase of intracellular cyclic GMP concentration.

SECRETORY AND VASCULAR EFFECTS OF THE OPTICAL ISOMERS OF NICARDIPINE

1. The effects of optical isomers of nicardipine on the secretion of pancreatic juice and blood flow were investigated in the dog‐isolated, blood‐perfused pancreas.