{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:08:51Z","timestamp":1778274531104,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,9,22]],"date-time":"2004-09-22T00:00:00Z","timestamp":1095811200000},"content-version":"vor","delay-in-days":2183,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[1998,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We examined the effects of noradrenaline on steady\u2010state intracellular pH (pH<jats:sub>i<\/jats:sub>) and the recovery of pH<jats:sub>i<\/jats:sub> from internal acid loads imposed by the NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup> prepulse technique in hippocampal CA1 neurones acutely dissociated from adult rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Under nominally HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2010free conditions, acid extrusion was accomplished by a Na<jats:sup>+<\/jats:sup>\u2010dependent mechanism, probably the amiloride\u2010insensitive variant of the Na<jats:sup>+<\/jats:sup>\u2010H<jats:sup>+<\/jats:sup> exchanger previously characterized in both fetal and adult rat hippocampal neurones. In the presence of external HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, acid extrusion appeared to be supplemented by a Na<jats:sup>+<\/jats:sup>\u2010dependent HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2010Cl<jats:sup>\u2212<\/jats:sup> exchanger, the activity of which was dependent upon the absolute level of pH<jats:sub>i<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Noradrenaline evoked a concentration\u2010dependent and sustained rise in steady\u2010state pH<jats:sub>i<\/jats:sub> and increased rates of pH<jats:sub>i<\/jats:sub> recovery from imposed intracellular acid loads. The effects of noradrenaline were not dependent upon the presence of external HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> but were blocked by substituting external Na<jats:sup>+<\/jats:sup> with <jats:italic>N\u2010<\/jats:italic>methyl\u2010D\u2010glucamine, suggesting that noradrenaline acts to increase steady\u2010state pH<jats:sub>i<\/jats:sub> by increasing the activity of the Na<jats:sup>+<\/jats:sup>\u2010H<jats:sup>+<\/jats:sup> exchanger.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effects of noradrenaline on steady\u2010state pH<jats:sub>i<\/jats:sub> and on rates of pH<jats:sub>i<\/jats:sub> recovery from imposed acid loads were mimicked by \u03b2<jats:sub>1<\/jats:sub>\u2010 and \u03b2<jats:sub>2<\/jats:sub>\u2010, but not \u03b1\u2010, adrenoceptor agonists. The \u03b2\u2010adrenoceptor antagonist propranolol blocked the ability of noradrenaline to increase both steady\u2010state pH<jats:sub>i<\/jats:sub> and rates of pH<jats:sub>i<\/jats:sub> recovery from acid loads.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effects of noradrenaline on steady\u2010state pH<jats:sub>i<\/jats:sub> and on pH<jats:sub>i<\/jats:sub> recovery rates following acid loads were not dependent on changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. However, the effects of noradrenaline were blocked by pre\u2010treatment with the adenylate cyclase inhibitor 2\u2032,5\u2032\u2010dideoxyadenosine and the cAMP\u2010dependent protein kinase inhibitors <jats:italic>R<\/jats:italic><jats:sub>p<\/jats:sub>\u2010adenosine\u20103\u2032,5\u2032\u2010cyclic monophosphorothioate (sodium salt; Rp\u2010cAMPS) and <jats:italic>N\u2010<\/jats:italic>[2\u2010(p\u2010bromocinnamylamino)ethyl]\u20105\u2010isoquinolinesulphonamide (H\u201089).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Forskolin, an activator of endogenous adenylate cyclase, and 3\u2010isobutyl\u20101\u2010methylxanthine, a phosphodiesterase inhibitor, mimicked the ability of noradrenaline to increase both steady\u2010state pH<jats:sub>i<\/jats:sub> and rates of pH<jats:sub>i<\/jats:sub> recovery from imposed acid loads, as did Sp\u2010cAMPS, a selective activator of cAMP\u2010dependent protein kinase. The effect of forskolin on steady\u2010state pH<jats:sub>i<\/jats:sub> was blocked by pre\u2010treatment with Rp\u2010cAMPS whereas the effect of Sp\u2010cAMPS was enhanced by pre\u2010treatment with the protein phosphatase inhibitor, okadaic acid.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Noradrenaline also increased steady\u2010state pH<jats:sub>i<\/jats:sub> and rates of pH<jats:sub>i<\/jats:sub> recovery from imposed acid loads in cultured postnatal rat hippocampal neurones. In this preparation, the effects of noradrenaline were occluded by 18\u201324 h pre\u2010treatment with cholera toxin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that noradrenaline increases the activity of the Na<jats:sup>+<\/jats:sup>\u2010H<jats:sup>+<\/jats:sup> exchanger in rat hippocampal neurones, probably by inducing an alkaline shift in the pH<jats:sub>i<\/jats:sub> dependence of the antiport, thereby raising steady\u2010state pH<jats:sub>i<\/jats:sub>. The effects of noradrenaline are mediated by \u03b2\u2010adrenoceptors via a pathway which involves the \u03b1\u2010subunit of the stimulatory G\u2010protein G<jats:sub>s<\/jats:sub> (G<jats:sub>s\u03b1<\/jats:sub>), adenylate cyclase, cAMP and the subsequent activation of cAMP\u2010dependent protein kinase which, in turn, may phosphorylate the exchange mechanism.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/j.1469-7793.1998.487be.x","type":"journal-article","created":{"date-parts":[[2004,9,22]],"date-time":"2004-09-22T07:56:18Z","timestamp":1095839778000},"page":"487-505","source":"Crossref","is-referenced-by-count":36,"title":["Effects of noradrenaline on intracellular pH in acutely dissociated adult rat hippocampal CA1 neurones"],"prefix":"10.1113","volume":"512","author":[{"given":"Garth A. 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