Yasuhiko Furuta

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

1 Effects of inhibitors of DOPA decarboxylase, dopamine β‐hydroxylase and monoamine oxidase, and haloperidol on the secretion of pancreatic juice induced by l‐DOPA and dopamine were studied in preparations of the isolated blood‐perfused canine pancreas. 2 The increased secretion induced by the infusion of l‐DOPA (100 μg/min) was completely antagonized by Ro 4–4602 (300 μg), a DOPA decarboxylase inhibitor. 3 The secretogogue effect of dopamine (1–10 μg) intra‐arterially was not affected by Ro 4–4602, but was enhanced by the infusion of fusaric acid (100 μg/min), a dopamine β‐hydroxylase inhibitor. 4 The increase in the secretion induced by dopamine (1–10 μg) was enhanced by treatment with nialamide (100 mg/kg), a monoamine oxidase inhibitor, given intravenously. 5 Haloperidol (1 mg) intra‐arterially attenuated the dopamine‐induced pancreatic secretion. 6 It is concluded that l‐DOPA is converted to dopamine in the acinar cells which causes an increase in the secretion of pancreatic juice, thus the intracellular level of dopamine may be controlled by enzymatic equilibrium.

Simultaneous determination of glyceryl trinitrate and its principal metabolites, 1,2- and 1,3-glyceryl dinitrate, in plasma by gas chromatography-negative ion chemical ionization-selected ion monitoring

A specific and sensitive method for the quantitation of glyceryl trinitrate (GTN) and its principal metabolites, 1,2- and 1,3-glyceryl dinitrate (GDN) in dog plasma by capillary gas chromatography-negative ion chemical ionization-selected ion monitoring using dichloromethane as a reagent gas and the corresponding compounds labelled with stable isotopes as internal standards. The quantitation limits of the method for GTN and the GDNs were 0.1 and 1.0 ng/ml in plasma, respectively. When GTN was administered intravenously to four anaesthetized beagle dogs at a dose of 6 micrograms/kg . min for 30 min, the plasma levels of GTN and 1,2- and 1,3-GDN reached a maximum at the end-point of infusion and decreased with bi-exponential decay. The half-lives of the alpha- and beta-phases were 0.50 and 4.95 for GTN, 8.10 and 40.6 for 1,2-GDN and 8.50 and 48.5 for 1,3-GDN, respectively.

MODIFICATION BY DRUGS OF THE SECRETAGOGUE EFFECT OF DOPAMINE ON THE PANCREAS

1 The 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 (100 μg, i.a.) stimulated the secretion but was far less potent than dopamine. Epinine (0.3–1 mg. i.a.), α‐methyldopamine (10–300 μg, i.a.) and octopamine (10–300 μg, i.a.) were ineffective. 3 α‐Methyldopa (30 mg, i.a.) inhibited the stimulating effect of l‐DOPA (1–3 mg) on pancreatic secretion. 4 Apomorphine (1 mg, i.a.) attenuated dopamine‐induced (1–30 μg) pancreatic secretion but did not antagonize secretin‐induced (0.03–0.3 units) or pancreozymin‐induced (0.3–1 units) 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 dogs treated with secretin, reserpine, l‐DOPA or α‐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.

Effect of depletion of serum calcium by EGTA on canine pancreatic secretion induced by dopamine and by secretin.

SUMMARY 1. Pancreatic secretion has been monitored in the isolated, blood‐perfused canine pancreas, and the effects of depletion of serum calcium by infusion of EGTA on the increases in secretion produced by intra‐arterial injections of dopamine and secretin have been investigated.

Effect of prostaglandin F2α on the secretion of pancreatic juice induced by secretin and by dopamine

Die Wirksamkeit von Prostaglandin F2α (PGF2α) auf die exokrine Pankreassekretion wurde an einem mit Blut perfundiereten Pankreas-Präparat des Hundes untersucht. PGF2α (100 μg) hemmte die durch Sekretin stimuliete, aber nicht die durch Dopamin stimulierte Sekretion.

l-dopa and pancreatic secretion

Abstract Greengard , Roback and Ivy (1942) first observed that epinine ( N -methyldopamine), dopamine (dihydroxyphenylethylamine) and few phenylethylamine derivatives given intravenously stimulated the canine pancreatic secretion, while the majority of sympathomimetic amines tested inhibited it. Although this observation appeared strikingly important, no particular attention had been given until Alm , Ehinger and Falck (1967) when Falck and his collaborators reported on the l -dopa turnover to dopamine in the mouse pancreas using fluorescense method. “After l -dopa i.v. first the whole of the pancreatic acinar cells displayed a specific diffuse fluorescence within few minutes and then most of the fluorescence was situated in zymogen granules as the second pattern of fluorescence after 40–60 min”. Thus, they assumed that l -dopa was decarboxylated to dopamine in the cytoplasm and then incorporated in granules. On the other hand, Holz , Credner and Strubing (1942) demonstrated the existence of dopa decarboxylase in the pancreas, and Schumann and Heller (1959) detected a relatively large amount of dopamine in the pancreas of the ox and the sheep.