Effects of cyclic adenosine monophosphate-dependent protein kinase and calcium-dependent protein kinase modulators on stimulated gastric acid secretion in the perfused rat stomach.
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.
Rotker
J D
JD
Department of Medicine, State University of New York-Health Science Center, Syracuse, USA.
Strapko
A
A
Nandi
J
J
Bosche
M C
MC
Levine
R A
RA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology
D007546:Isoquinolines; D009281:Naphthalenes; D010879:Piperazines; D013449:Sulfonamides; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010418:Pentagastrin; C058819:calphostin C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium