Secretory and Vascular Response to Various Biogenic and Foreign Substances of the Perfused Canine Pancreas

Takeuchi, Osamu; Satoh, Susumu; Hashimoto, Koroku

doi:10.1254/jjp.24.57

Cited by 35 publications

(25 citation statements)

References 23 publications

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“…Hashimoto and collaborators demonstrated that exogenous dopamine increases the secretion of pancreatic juice, of which the components are similar to those induced by exogenous secretin (2), and that there are specific dopamine receptors related to the exocrine pancreatic secretion in dogs (3)(4)(5)(6). Thus, the dopamine receptor response can be easily quantified by measuring the increases in volume of the pancreatic juice.…”

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confidence: 99%

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Satoh

Honda

1980

Japanese Journal of Pharmacology

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Abstract-The inhibitory effect of sulpiride on dopamine receptors was investigated in the exocrine pancreas of dogs anesthetized with pentobarbital and with the stomach ligated at the pylorus. All test substances were given intravenously. Dopamine, acetylcholine, histamine and secretin produced a dose-related increase in pancreatic juice secretion, though the dose-effect curves of these secretagogues differed in shape. Epinephrine, norepinephrine, isoproterenol, methamphetamine and serotonin had no secretagogue effects. The effects of acetylcholine and histamine were inhibited by atropine and cimetidine, respectively. The effect of dopamine was blocked by halo peridol, but not by atropine, cimetidine, phentolamine and propranolol. These results suggest that dopamine acts on specific dopamine receptors related to the exocrine pancreatic secretion.Haloperidol had no effect on the effects of acetylcholine and histamine, but did inhibit the secretin-induced secretion, though the inhibitory effect was to a lesser extent than on the dopamine response. Sulpiride and chlorpromazine also suppressed dose-dependently the dopamine-induced secretion. The inhibitory activity of sulpiride was almost the same as that of haloperidol, and 12 times more potent than that of chlorpromazine.Sulpiride was found to be a potent dopamine antagonist in the canine exocrine pancreas.In a previous report we showed that sulpiride`, an antipsychotic drug, has essentially a potent inhibition on dopamine receptors in the central nervous system. This drug, when given intraventricularly to rats, was equally or more effective than haloperidol in inducing catalepsy and in inhibiting apomorphine and methamphetamine-induced circling behavior (1). The present paper deals with antagonism of sulpiride to dopamine in the exocrine pancreas of dogs.Hashimoto and collaborators demonstrated that exogenous dopamine increases the secretion of pancreatic juice, of which the components are similar to those induced by exogenous secretin (2), and that there are specific dopamine receptors related to the exocrine pancreatic secretion in dogs (3-6). Thus, the dopamine receptor response can be easily quantified by measuring the increases in volume of the pancreatic juice. This system is a convenient tool for studies on the interaction between dopamine and test substances.We attempted to evaluate the antidoparnine activity of sulpiride, chlorpromazine and haloperidol given to anesthetized dogs before an i.v. administration of dopamine in order to evoke increased pancreatic secretion. We also examined the specificity of the pancreatic dopamine receptor response to dopamine injected systemically, as the dopamine receptor

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confidence: 99%

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Satoh

Honda

1980

Japanese Journal of Pharmacology

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“…Case and Scratcherd (10) reported that the secretory response to secretin was accompanied by an increase in the cytoplasmic levels of cyclic AMP. Dibutyryl cyclic AMP given intra-arterially also caused the secretion of pancreatic juice (2). These results suggest that cyclic AMP acts as a second messenger or a mediator of secretin.…”

mentioning

confidence: 67%

“…This preparation is convenient as a tool for studying the direct actions of drugs on the pancreas (2). Recently, we reported that a potent vasodilator, papaverine, caused a secretion of pancreatic juice in dogs (3).…”

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confidence: 99%

Potentiating effects of dipyridamole on the secretion of pancreatic juice induced by secretin in the blood-perfused dog pancreas.

1982

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“…(20), and also showed that the dog and rat exocrine pancreas responded differently to 5-HT and histamine. On the basis of data reported thus far (7,9,20,21, and present results), the main differences between dogs and rats in the response to various amines can be summarized as follows: 1) DA has a potent stimulatory effect in dogs while DA has only a weak stimulatory effect on the protein secretion and a very weak stimulatory effect on the rate of flow in rats, 2) 5-HT has inhibitory effects on the rate of flow and protein secretion in rats, but no effect in dogs, 3) o-agonists decrease the rate of flow in rats, but have no effects in dogs, 4) j-agonist has a profound stimulatory effect on the rate of flow in rats, but has no effect in dogs, and 5) histamine is a effective stimulant in dogs, but not in rats.…”

Section: Discussionmentioning

confidence: 93%

“…Accordingly, the receptor mechanism for the rate of flow could not be clarified. However, it is apparent that the stimulatory effects of DA on the exocrine pancreas in rats are weak as opposed to the strong secretin-like effects in dogs (7,(10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Amines and the rat exocrine pancreas. 3. Effects of amines on pancreatic secretion.

Mori

Satoh

et al. 1979

Jpn.J.Pharmacol

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Abstract-Effectsof L-dopa, L-5HTP, a few amines, and related compounds on the pancreatic rate of flow, protein secretion, and bicarbonate secretion were studied in conscious rats. Single injections of L-dopa, DA and apomorphine did not modify the rate of flow, while an increase was seen with infusion of DA. L-dopa stimulated the protein secretion. L-5HTP and 5-HT decreased the rate of flow and protein secretion. Effects of L-dopa and L-5HTP on the protein secretion were prevented by DA and 5-HT blockers, respectively. Neither L-dopa nor L-5HTP had any effect on the bicarbonate secretion. Secretin and cholinergic agents (acetylcholine and carbamyl choline) strongly stimulated the rate of flow of pancreatic juice. a-Agonists (phenyl ephrine and clonidine) decreased the rate of flow, and the effects were inhibited by an a-blocker. The a-agonists had no effect on protein secretion. Although, a-blockers (phenoxybenzamine and phentolamine) had no effects on the rate of flow, they did decrease the protein secretion.Isoproterenol was a potent secretagogue, and the effect was suppressed by a f4-blocker. Histamine had no effect on the rate of flow. The results were discussed in relation to our previous histochemical and chemical findings, and the species difference between rats and dogs in response to the amines.Acinar cells of the exocrine pancreas of rats efficiently take up and metabolize L-dopa (1, 2) and L-5HTP (3, 4). In previous histochemical and chemical studies, some differences and similarities between the L-dopa and L-5HTP metabolism were observed. The main findings were: 1) L-dopa was more rapidly metabolized than L-5HTP, 2) the pretreatment with DA-blockers increased markedly the accumulation of pancreatic DA after injection of L-dopa, whereas pretreatment with 5-HT blocker decreased the accumulation of 5-HT after injection of L-5HTP, 3) the pretreatment with a-blocker resulted in the increase of both DA and 5-HT content after injection of L-dopa and L-5HTP, respectively, and 4) iproniazide, a MAO inhibitor, was more effective in increasing the accumulation of 5-HT.The excretion of DA and 5-HT appeared to be associated with the secretion of zymogen granules, thus the amines can serve as indicator of pancreatic secretory activity, particularly enzyme secretion. Because DA and 5-HT blockers produced an increase and decrease in accumulation of pancreatic DA and 5-HT contents, respectively, it was suggested that DA and 5-HT, formed from their corresponding precursors, could modify the pancreatic secretion of rats, particularly enzyme secretion.The present experiments were an attempt to correlate the histochemical and chemical findings with possible pharmacological effects of L-dopa, L-5HTP, their corresponding amines, and the blockers on the pancreatic secretion of rats. Effects of other amines were also studied.

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Secretory and Vascular Response to Various Biogenic and Foreign Substances of the Perfused Canine Pancreas

Cited by 35 publications

References 23 publications

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Potentiating effects of dipyridamole on the secretion of pancreatic juice induced by secretin in the blood-perfused dog pancreas.

Amines and the rat exocrine pancreas. 3. Effects of amines on pancreatic secretion.

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