Interactions between Ca2+- and cAMP-dependent stimulatory pathways in parietal cells.
Isolated rat parietal cells were used to investigate the role of intracellular Ca2+ in the action of cAMP-dependent secretagogues and cross talk between cAMP- and Ca2+ -dependent stimulatory pathways. Aminopyrine accumulation (an index of acid produced and trapped by the parietal cells), cytosolic free Ca2+, morphological transformation and cell viability were used to investigate parietal cell function and stimulation. The increase of cytosolic free Ca2+ promoted by gastrin, or carbachol, was abolished by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA, 10 microM). Also, the morphological transformations induced by dibutyryladenosine 3':5'-cyclic monophosphate (DBcAMP), gastrin, and Sp-adenosine-cyclic-3', 5'-monophosphothioate (Sp-cAMPS) were completely abolished by BAPTA (10 microM). In aminopyrine accumulation the action of 1 mM DBcAMP was dose-dependently reduced by BAPTA. The Ca2+ ionophore A23187 alone, in the range of 1 pM to 1 microM, had no effect but it dose-dependently potentiated the action of 1 mM DBcAMP in aminopyrine accumulation. The inhibitory actions of BAPTA on DBcAMP- and histamine-stimulated aminopyrine accumulation were dose-dependently reversed by A23187. Histamine-stimulated protein kinase activity and viability parameters as cellular lactate dehydrogenase (LDH) and trypan blue exclusion were not changed by BAPTA. These results indicated that in isolated parietal cells: (1) the action of cAMP-dependent secretagogues in aminopyrine accumulation and morphological transformation are dependent on cytosolic free Ca2+; (2) Ca2+ -induced morphological transformation is essential for aminopyrine accumulation; (3) a threshold level of one second messenger is required for stimulation of aminopyrine accumulation by the other second messenger.
Li
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Department of Cell Biology, Faculty of Health Sciences Linköping University, Sweden.
Mårdh
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D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction
D007476:Ionophores; D000632:Aminopyrine; D000001:Calcimycin; D006632:Histamine; D000242:Cyclic AMP; D002118:Calcium