Effects of cyclic adenosine monophosphate-dependent protein kinase and calcium-dependent protein kinase modulators on stimulated gastric acid secretion in the perfused rat stomach

• Published in: Pharmacology Vol. 51; no. 4; p. 263
• Main Authors: Rotker, J D, Strapko, A, Nandi, J, Bosche, M C, Levine, R A
• Format: Journal Article
• Language: English
• Published: Switzerland 01.10.1995
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Administration, Oral; Animals; Calcium - metabolism; Cyclic AMP - pharmacology; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - physiology; Gastric Acid - secretion; Histamine - administration & dosage; Histamine - pharmacology; Injections, Intravenous; Isoquinolines - administration & dosage; Isoquinolines - pharmacology; Male; Naphthalenes - administration & dosage; Naphthalenes - pharmacology; Pentagastrin - administration & dosage; Pentagastrin - pharmacology; Piperazines - administration & dosage; Piperazines - pharmacology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Rats; Rats, Sprague-Dawley; Sulfonamides; Tetradecanoylphorbol Acetate - administration & dosage; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0031-7012
• DOI: 10.1159/000139368

The effects of cyclic adenosine monophosphate-dependent protein kinase (PKA) and calcium-dependent protein kinase (PKC) modulators on secretagogue-stimulated gastric acid secretion were studied in the continuously perfused stomach of the anesthetized rat. Intravenous histamine (0.25 mg/kg/h) and pentagastrin (2 micrograms/kg/h) increased secretion above baseline by three- and fourfold, respectively. Parenteral administration of a PKC activator, 12-o-tetradecanoylphorbol-13-acetate (TPA; 0.1 nmol/h), decreased histamine- and pentagastrin-stimulated secretion by 64 and 40%, respectively. Administration of PKC inhibitors, calphostin C and 1-(5-isoquinolinyl sulfonyl)-2 methylpiperazine (H-7; 10 nmol/h, each), increased histamine- and pentagastrin-stimulated secretion by 115 and 74% and 42 and 79%, respectively, while equimolar concentrations (10 nmol/h) of three other isoquinoline sulfonamides (HA-1004, H-8, and H-89) had no effect, except for H-89 (100 nmol/h) which inhibited the histamine- and penta-gastrin-stimulated acid secretion by 44%. Basal secretion was not significantly altered by the aforementioned drugs. The TPA-induced inhibition of pentagastrin-stimulated secretion was partially reversed by treatment with H-7. These findings support a role of PKA and PKC in the modulation of stimulated gastric acid secretion in vivo.