Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Roles of Ca2+ and protein kinase C (PKC) in the regulation of acid/base transport in isolated rabbit proximal tubules were investigated by measuring cytosolic Ca2+ concentrations ([Ca2+]i) and cell pH (pHi) with fluorescent probes. Ionomycin (0.2 microM) increased [Ca2+]i by approximately 200 nM but did not affect the basolateral Na(+)-HCO3- cotransporter. However, the apical Na+/H+ exchanger was inhibited by 50% by ionomycin, and this inhibition was abolished either by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular Ca2+ chelator, or by KN-62, an inhibitor of calcium-calmodulin-dependent protein kinase II (CaM kinase II). On the other hand, phorbol 12-myristate 13-acetate (PMA, 0.5 microM) did not affect the apical Na+/H+ exchanger but did stimulate the basolateral Na(+)-HCO3- cotransporter by 60-80%, and this stimulation was prevented by calphostin C, an inhibitor of PKC. Consistent with the cotransporter stimulation, PMA decreased steady-state pHi in the presence of CO2/ HCO3-. These results indicate that 1) the acute increase in [Ca2+]i within physiological ranges inhibits the apical Na+/H+ exchanger, probably through mediation of CaM kinase II; and 2) the short-term PKC activation stimulates the basolateral Na(+)-HCO3- cotransporter.
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PMID:Roles of Ca2+ and PKC in regulation of acid/base transport in isolated proximal tubules. 894 2

Fluid and ion transport across biliary epithelium contributes to bile flow. Alterations of this function may explain hepatobiliary complications in cystic fibrosis (CF). We investigated electrogenic anion transport across intact non-CF and CF human gallbladder mucosa in Ussing-type chambers. In non-CF tissues, baseline transmural potential difference (PD), short-circuit current (Isc), and resistance (R) were -2.2 +/- 0.3 mV (lumen negative), 40.7 +/- 7.8 microA/cm2, and 66.5 +/- 9.6 Omega. cm2, respectively (n = 14). The addition of forskolin (10(-5) mol/L) to the apical and basolateral baths and that of adenosine 5'-triphosphate (ATP) (10(-4) mol/L) to the apical bath induced significant increases in Isc by 8.0 +/- 1.4 and 10.3 +/- 1.8 microA/cm2, respectively. Depletion of bathing solutions in Cl- and HCO3- significantly reduced baseline Isc and the forskolin- and ATP-induced increases in Isc. Anion secretion was stimulated by extracellular ATP via P2Y2 purinoceptors, as indicated by the effects of different nucleotides on Isc and on 36Cl efflux in cultured gallbladder epithelial cells. This effect was mediated by cytosolic calcium increase and Ca2+/calmodulin-dependent protein kinase II, as ascertained by using inhibitors. In CF preparations, basal PD and Isc were lower than in non-CF, and the response to forskolin was abolished, whereas the response to ATP was enhanced (P <.05 for all). We conclude that electrogenic anion secretion occurs in human gallbladder mucosa under basal state and is stimulated by an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway mediated by cystic fibrosis transmembrane conductance regulator (CFTR), and by exogenous ATP via a CFTR-independent pathway that is up-regulated in CF and involves P2Y2 purinoceptors and a calcium-dependent pathway.
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PMID:Regulation of electrogenic anion secretion in normal and cystic fibrosis gallbladder mucosa. 986 42