Na+-dependent elevation of the acidic cell surface pH (microclimate pH) of rat jejunal villus cells induced by cyclic nucleotides and phorbol ester: possible mediators of the regulation of the Na+/H+ antiporter.
The effects of cyclic nucleotides and phorbol ester on the acidic cell surface pH of rat jejunal villi were studied by using single-barrelled pH-sensitive microelectrodes. Addition of dibutyryl cAMP (1 mM) to the mucosal bathing solution caused an elevation of the cell surface pH from 6.19 +/- 0.04 (n = 12 measurements from three animals) to 6.53 +/- 0.03 (12) in the presence of Na+ in the medium. However, dibutyryl cAMP had no significant effect in the absence of Na+ and presence of 1 mM amiloride. Dibutyryl cGMP (1 mM) also had an Na+-dependent inhibitory effect on the cell surface pH. A phorbol ester, phorbol 12-myristate 13-acetate, caused an elevation of the cell surface pH only in the presence of Na+ from 6.14 +/- 0.07 (12) to 6.46 +/- 0.08 (12). Phorbol and phorbol 13-acetate, which do not stimulate protein kinase C, were without significant effects. These results suggest that increased levels of the intracellular cyclic nucleotides and activation of protein kinase C raise the acidic cell surface pH by inhibiting the activity of the brush-border Na+/H+ antiporter in the rat jejunal villus cells.
Shimada
T
T
Department of Physiology, Faculty of Medicine, University of Tokyo, Japan.
Hoshi
T
T
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D015232:Dinoprostone; D006863:Hydrogen-Ion Concentration; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D002352:Carrier Proteins; D010703:Phorbol Esters; D010704:Phorbols; D011458:Prostaglandins E; D017923:Sodium-Hydrogen Exchangers; D003995:Dibutyryl Cyclic GMP; D000001:Calcimycin; D003994:Bucladesine; D000584:Amiloride; D012964:Sodium; D013806:Theophylline; D006152:Cyclic GMP; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; C033085:phorbol