Effects of enzyme inhibitors of catecholamine metabolism and of haloperidol on the pancreatic secretion induced by <scp>l</scp>‐DOPA and by dopamine in dogs

Furuta, Yasuhiko; Hashimoto, Koroku; Iwatsuki, Kazuhiko; Takeuchi, Osamu

doi:10.1111/j.1476-5381.1973.tb08160.x

Cited by 45 publications

(30 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…* Presented in part at the 13 During investigations on monoaminergic mechanisms in pancreatic islets we employed the dopaminergic antagonist haloperidol, which is purported to be a specific dopamine receptor blocking agent in tissues such as brain [5], exocrine pancreas [6] and renal and mesenteric vessels [7]. Using the isolated, perfused canine pancreas it was noted that this dopaminergic antagonist inhibited release of both glucagon and insulin.…”

mentioning

confidence: 99%

Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas

Hermansen¹

1978

Diabetologia

View full text Add to dashboard Cite

Summary. The effect of haloperidol, a dopaminergic antagonist, on insulin and glucagon secretion was investigated using the isolated, perfused canine pancreas. Haloperidol at 4 x 10 .7 to 10 .5 mol/1 caused a dose-dependent inhibition of glucagon release both at low (25 mg/100 ml) and high glucose concentrations (150 mg/100 ml). At the low glucose concentration insulin release was already maximally suppressed. At the high glucose concentration haloperidol (4 × 10 -7 to 10 .5 mol/1) also caused a dosedependent inhibition of insulin release. Haloperidol (10 -5 mol/1) inhibited dramatically pancreatic A and B cell responses to isoproterenol (2 ng/ml), acetylcholine (1 ~tmol/1) and arginine (5mmol/1). The inhibitory effect of haloperidol on both glucagon and insulin release could be eliminated by increasing perfusate calcium concentration from 1.3 to 8.8 mmol/1. These findings suggested that haloperidol blocks glucagon and insulin release in a somatostatin-like manner by affecting a fundamental step of the stimulus-secretion coupling, probably by interfering with calcium handling of the pancreatic A and B cells.Key words: Isolated, perfused canine pancreas, haloperidol, acetylcholine, isoproterenol, arginine, calcium, somatostatin-like inhibition, insulin secretion, glucagon secretion.Falck and Hellman [1,2] have demonstrated that in many species the endocrine pancreatic cells contain monoamines, particularly serotonin and dopamine [3,4]. The physiological significance of these monoamines stored within the islet cells is unknown.* Presented in part at the 13 th Annual Meeting of the European Association for the Study of Diabetes, Geneva, Switzerland, September 1977During investigations on monoaminergic mechanisms in pancreatic islets we employed the dopaminergic antagonist haloperidol, which is purported to be a specific dopamine receptor blocking agent in tissues such as brain [5], exocrine pancreas [6] and renal and mesenteric vessels [7]. Using the isolated, perfused canine pancreas it was noted that this dopaminergic antagonist inhibited release of both glucagon and insulin.The purpose of the present study was to investigate further the effect of haloperidol on insulin and glucagon secretion from the isolated, perfused canine pancreas in order to elucidate the mechanisms by which this substance produces its bihormonal inhibitory actions. Material and MethodsMongrel dogs, fasted overnight, weighing 18-25 kg were used as pancreas donors. The technique for isolation of the canine pancreas and the perfusion system have been described in detail by Iversen [8,9]. In brief, the preparation consisted of the pancreas and the proximal 10 cm of the attached duodenum. A nonrecirculating medium consisting of a Krebs Ringer bicarbonate buffer containing dextran 40 g/1 (MW 75,000), 2 g/1 bovine albumin, glutamate, fumarate and pyruvate, each at a concentration of 5 mmol/l was introduced through the splenic and the coeliac arteries, and the total portal effluent was collected every 1 min. Oxygenation of the Krebs-Ringer bicarbo...

show abstract

mentioning

confidence: 99%

Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas

Hermansen¹

1978

Diabetologia

View full text Add to dashboard Cite

show abstract

“…The responses to dopamine were modified by haloperidol, a dopamine receptor antagonist (6). We suggested that there were specific receptors for the secretion of the pancreatic juice by dopamine and that dopamine may play a physiological role in the secretory mechanism of the dog pancreas.…”

mentioning

confidence: 89%

“…Details of the preparation have been described elsewhere (4,6). The rate of pancreatic secretion was measured using a drop counter.…”

mentioning

confidence: 99%

Effect of acetazolamide on the secretion of pancreatic juice induced by dopamine in dogs.

Iwatsuki

Chiba

1981

Jpn.J.Pharmacol

View full text Add to dashboard Cite

“…The pancreas was perfused with the animal's own blood from the femoral artery as described previously (Hashimoto et al, 197 1;Furuta et al, 1973). The rate of the exocrine secretion of the pancreas was measured by a drop counter and the blood flow was monitored by a magnetic flowmeter (Nihon Kohden MF-46).…”

Section: Methodsmentioning

confidence: 99%

“…This observation gained new interest when Alm, Ehinger & Falck (1969) observed a rapid turnover of 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) to 3-hydroxytyramine (dopamine) in the pancreas and Hashimoto, Satoh & Takeuchi (1971) confirmed the potent effect of L-DOPA and dopamine on exocrine pancreatic secretion. Furthermore it was found (Furuta, Hashimoto, Iwatsuki & Takeuchi, 1973) that the effect of L-DOPA was depressed by inhibitors of dopa decarboxylase whereas the effect of dopamine was potentiated by inhibitors of monoamine oxidase and diminished by haloperidol, a dopamine receptor blocking drug. No changes in pancreatic secretion were observed after injections of ephedrine, phenylephrine, methoxamine and tyramine (Takeuchi, Satoh & Hashimoto, 1973).…”

Section: Introductionmentioning

confidence: 99%

Modification by Drugs of the Secretagogue Effect of Dopamine on the Pancreas

Furuta

Hashimoto

Ishíi

et al. 1974

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

IThe specific stimulating action of dopamine and L-DOPA on exocrine pancreatic secretion was further investigated in the isolated blood-perfused canine pancreas. 2 6-Hydroxydopamine (I100 ig, i.a.) stimulated the secretion but was far less potent than dopamine. Epinine (0.3-1mg. i.a.), a-methyldopamine (10-300 ,g, i.a.) and octopamine (10-300 pg, i.a.) were ineffective. secretion. 5 These observations suggest that L-DOPA is probably converted to dopamine to stimulate the exocrine pancreas, and that dopamine interacts with the specific receptors. 6 The noradrenaline and dopamine content of the canine pancreas was estimated in controls and in do,gs treated with secretin, reserpine, L-DOPA or ca-methyldopa. The values for dopamine and noradrenaline in controls were 139 ± 6 and 375 ± 40 ng/g tissue (n=13), respectively. Reserpine reduced the noradrenaline content of the pancreatic tissue without affecting the dopamine content. L-DOPA or secretin caused a significant increase in the dopamine, but not in the noradrenaline content. It is suggested that dopamine has a physiological function in the pancreas which is independent of that of the noradrenaline-containing nerve fibres.

show abstract

Effects of enzyme inhibitors of catecholamine metabolism and of haloperidol on the pancreatic secretion induced by l‐DOPA and by dopamine in dogs

Cited by 45 publications

References 13 publications

Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas

Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas

Effect of acetazolamide on the secretion of pancreatic juice induced by dopamine in dogs.

Modification by Drugs of the Secretagogue Effect of Dopamine on the Pancreas

Contact Info

Product

Resources

About