Inhibitory effect of phorbol 12,13 dibutyrate on carbachol-activated nonselective cationic current in guinea-pig gastric myocytes.
The effect of protein kinase C (PKC) on carbachol (CCh)-activated nonselective cationic current (ICCh) was investigated in guinea-pig gastric myocytes using a PKC activator, phorbol 12, 13 dibutyrate (PDBu). Pretreatment with 1 micro M PDBu suppressed ICCh by 96.5 +/- 2.9% (n = 14) in a reversible manner in nystatin-perforated mode. In the presence of 1 microM chelerythrine, a PKC inhibitor, inhibition of ICChby PDBu was not seen. In whole-cell mode, the inhibition of ICCh by PDBu was dependent on intracellular MgATP. In the presence of MgATP in the pipette, PDBu decreased ICCh by 98.8 +/- 1.2% (n = 5) as was observed in nystatin-perforated mode. However, PDBu had little effect on ICCh in the absence of MgATP in the pipette; the extent of inhibition was 12.7 +/- 4.3% (n = 8). PDBu also suppressed the generation of cationic current induced by intracellularly perfused GTP[gammaS]. In the PDBu-pretreated group (n = 9) and PDBu-untreated control group (n = 6), GTP[gammaS]-induced currents were 6.7 +/- 2.4 pA and 236 +/- 23 pA, respectively. These results suggest that PKC modulates ICCh at postreceptor sites via protein phosphorylation.
Ahn
S C
SC
Department of Physiology & Biophysics, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Korea.
Kim
S J
SJ
So
I
I
Kim
K W
KW
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism*; D004553:Electric Conductivity; D005753:Gastric Mucosa / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D013270:Stomach / Q000166:cytology / Q000502:physiology*
D002412:Cations; D007473:Ion Channels; D018721:Muscarinic Agonists; D015240:Phorbol 12,13-Dibutyrate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002217:Carbachol