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.
Iwatsuki
K
K
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Ren
L M
LM
Chiba
S
S
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010189:Pancreatic Juice / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D044005:Tetrahydroisoquinolines
D001552:Benzazepines; D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C073504:zelandopam; D004298:Dopamine