Effects of methylisobutylxanthine (MIX) on the secretion of pancreatic juice in the blood-perfused canine pancreas.

Iwatsuki, Kazuhiko; Iijima, Fujio; Chiba, Shigetoshi

doi:10.1254/jjp.32.384

Cited by 6 publications

(7 citation statements)

References 8 publications

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“…This action of ZSY-27 resembled that of secretin and dopamine (Table 2), since ZSY-27 increases the volume of juice and bicarbonate concentration but had little effect on the protein secretion Furuta et al 1972). The secretory potency of ZSY-27 and the other phosphodiesterase inhibitors cited here (Iwatsuki & Chiba 1980;Iwatsuki et al 1982a) may be arranged in the following order: dopamine > methylisobutylxanthine > ZSY-27 = papaverine > aminophylline (Fig. 4).…”

Section: Discussionmentioning

confidence: 81%

“…Blocking agents were injected intra-arterially 2 min before the injection of ZSY-27. The doses administered were enough to block the action of its agonist (Iwatsuki et al 1982a); 100 pg of phentolamine, 300 pg of propranolol, 1OOpg of atropine, 1 mg of sulpiride and 1 mg of cimetidine in each three to four experiments. None of these agents appreciably altered the secretory or vascular responses to ZSY-27 (1 mg).…”

Section: Effects Of Several Blocking Agents On Zsy-27-induced Pancreamentioning

confidence: 99%

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Effects of a Synthesized Phosphodiesterase Inhibitor, Zsy‐27, on Pancreatic Exocrine Secretion of the Dog

Iwatsuki

Yamagishi

Chiba

1986

Clin Exp Pharma Physio

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The effects of a synthesized phosphodiesterase inhibitor, ZSY-27, on the secretion of pancreatic juice were investigated in dog isolated and blood-perfused pancreas, and compared with those of secretin and dopamine. Intravenous administration of ZSY-27 (0.3-1 mg/kg) elicited increases in pancreatic secretion. Intra-arterial (i.a.) administration of ZSY-27 (0.1-1 mg) also elicited increased secretion. The secretory activity of ZSY-27 (1 mg) was approximately equal to that of 0.1 units of secretin and 2.5 micrograms of dopamine. The concentration of bicarbonate in the pancreatic juice induced by ZSY-27 i.a. was increased, but the protein concentration was not increased significantly. These effects are analogous to those of secretin and dopamine. ZSY-27-induced pancreatic secretion was not modified by pretreatment with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced secretion was significantly potentiated by infusion of ZSY-27 (25 micrograms/min) but dopamine-induced one was not. These results suggest that ZSY-27 increases pancreatic secretion acting directly on the ductular cells of the dog pancreas, at least in part, through the increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.

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Section: Discussionmentioning

confidence: 81%

Section: Effects Of Several Blocking Agents On Zsy-27-induced Pancreamentioning

confidence: 99%

Effects of a Synthesized Phosphodiesterase Inhibitor, Zsy‐27, on Pancreatic Exocrine Secretion of the Dog

Iwatsuki

Yamagishi

Chiba

1986

Clin Exp Pharma Physio

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“…Phosphodiesterase (PDE) inhibitors such as papaverine, theophylline and 3-isobutyl-lmethylxanthine (IBMX) were also shown to stimulate pancreatic secretion (Takeuchi el al. 1974;Iwatsuki & Chiba 1980;Iwatsuki et al 1982a). Thus, cyclic AMP may be an intracellular mediator in the process of pancreatic secretion.…”

Section: Introductionmentioning

confidence: 99%

“…Ro20,1724 and rolipram inhibit PDE IV and zaprinast inhibits PDE V, although selective PDE I1 inhibitors have not been found. Such PDE inhibitors produce a wide variety of effects, including pancreatic secretion (Takeuchi et al 1974;Iwatsuki & Chiba 1980;Iwatsuki et al 1982a;Iwatsuki et al 1991). However, there are no available reports of Ro20,1724 effects on pancreatic exocrine secretion.…”

Section: Introductionmentioning

confidence: 99%

EFFECTS OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE IV INHIBITOR, Ro20,1724, ON PANCREATIC EXOCRINE SECRETION IN DOG

Iwatsuki

Ren

Chiba

1994

Clin Exp Pharma Physio

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1. The effects of the cyclic nucleotide phosphodiesterase (PDE) inhibitors, Ro20,1724, 3-isobutyl-1-methylxanthine (IBMX), trifluoperazine (TFP) and amrinone on pancreatic exocrine secretion were investigated in anaesthetized dogs in comparison with those of secretion and cholecystokinin octapeptide (CCK-8). 2. Ro20,1724 (1-30 nmol/kg), IBMX (3-30 nmol/kg), secretin (0.01-0.1 pmol/kg) or CCK-8 (0.1-1 pmol/kg) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but TFP and amrinone (up to 1 mumol/kg) did not. 3. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by Ro20,1724, IBMX and secretin. Cholecystokinin octapeptide increased the protein concentration but did not alter the bicarbonate concentration. 4. Ro20,1724 and IBMX elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with Ro20,1724 and IBMX were additive. 5. Ro20,1724 and IBMX increased cyclic AMP concentration but did not affect cyclic GMP concentration. 6. These results suggest that Ro20,1724 and IBMX have secretory properties on pancreatic exocrine glands of the dog, which may be mediated through an increase in cyclic AMP subsequent to inhibition of PDE activity. Furthermore, pancreatic PDE enzymes in the dog may be mainly type IV.

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“…Additionally, secretin stimulated the pancreatic secretion concomi tant with the increase in the cyclic AMP con tent in the pancreas (3,4). Phosphodiesterase inhibitors such as theophylline, papaverine and 3-isobutyl-1-methylxanthine (IBMX) were also shown to stimulate the pancreatic secretion (2,5,6). Thus, cyclic AMP may be an intracellular mediator in the process of pancreatic secretion.…”

mentioning

confidence: 99%

Effects of DN-9693, a synthesized phosphodiesterase inhibitor, on pancreatic exocrine secretion in dogs.

et al. 1989

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Abstract-The effects of DN-9693, a synthesized phosphodiesterase inhibitor, on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas. DN-9693 injected intraarterially caused a dose-dependent increase in the secretion of pancreatic juice and decrease in the perfusion pressure.The threshold doses to increase the pancreatic secretion and to decrease the perfusion pressure were about 100 ,ug and 1 ,cg, respectively. Thus, the secretory response was less effective than the vascular response.The secretory activity of was approximately equal to that of 0.03 mg of 3 isobutyl-1 -methylxanthine, 0.5 mg of papaverine, 5 mg of theophylline, 0.08 units of secretin and 0.2 units of cholecystokinin.The concentration of bicarbonate in the pancreatic juice induced by DN-9693 was increased, but protein concentration was not. DN-9693-induced pancreatic secretion was not modified by pretreat ments with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin induced pancreatic secretion was significantly potentiated by infusion of DN-9693 (10 ,eg/min), but cholecystokinin-induced one was not. From these results, it is concluded that DN-9693 may produce an increase in pancreatic secretion by acting directly on the pancreatic exocrine gland of the dog, which might be mediated through an increase of intracellular cyclic AMP concentration by inhibiting phos phodiesterase activity.It was reported that adenosine 3",5 cyclic monophosphate (cyclic AMP) stimulated the pancreatic secretion of water and electrolytes in cats and dogs (1, 2). Additionally, secretin stimulated the pancreatic secretion concomi tant with the increase in the cyclic AMP con tent in the pancreas (3, 4). Phosphodiesterase inhibitors such as theophylline, papaverine and 3-isobutyl-1-methylxanthine (IBMX) were also shown to stimulate the pancreatic secretion (2, 5, 6). Thus, cyclic AMP may be an intracellular mediator in the process of pancreatic secretion. Along this line, it is of interest to investigate the effect of phospho diesterase inhibitors on pancreatic secretion. (1,5-dihydro-7-(1-piperidinyl) imidazo[2,1-b]quinazoline-2(3H)-one dihy drochloride hydrate) is a newly synthesized phosphodiesterase inhibitor and its potency was about 5 times as potent as papaverine in platelets (7). However, there is no available reports on the effect of DN-9693 on pancre atic exocrine secretion. The present experi ments were, therefore, undertaken to inves tigate the effects of DN-9693 on pancreatic secretion in isolated and blood-perfused day pancreas preparations in situ and to compare DN-9693 with secretin and cholecystokinin in the same preparations. Materials and MethodsTwenty-two mongrel dogs of either sex, weighing from 12-16 kg, were fasted 24 hr and anesthetized with sodium pentobarbital (30 mg/kg, i.v.). During the experimental periods, anesthesia was maintained by ad ditional injection of sodium pentobarbital (5 mg/kg, i.m.) at hourly intervals. The dogs

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Effects of methylisobutylxanthine (MIX) on the secretion of pancreatic juice in the blood-perfused canine pancreas.

Cited by 6 publications

References 8 publications

Effects of a Synthesized Phosphodiesterase Inhibitor, Zsy‐27, on Pancreatic Exocrine Secretion of the Dog

Effects of a Synthesized Phosphodiesterase Inhibitor, Zsy‐27, on Pancreatic Exocrine Secretion of the Dog

EFFECTS OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE IV INHIBITOR, Ro20,1724, ON PANCREATIC EXOCRINE SECRETION IN DOG

Effects of DN-9693, a synthesized phosphodiesterase inhibitor, on pancreatic exocrine secretion in dogs.

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