The release of intracellular Ca2+ in lacrimal acinar cells by alpha-, beta-adrenergic and muscarinic cholinergic stimulation: the roles of inositol triphosphate and cyclic ADP-ribose.

Abstract

Stimulation of rat lacrimal acinar cells with acetylcholine (ACh) and the beta-adrenergic agonist isoprenaline causes a rapid increase in inositol phosphates with 1-4 phosphate groups, resulting in release of Ca2+ from intracellular stores. Stimulation with the alpha-adrenergic agonist phenylephrine, however, causes a release of Ca2+ from internal stores which is 36% of that observed with ACh stimulation, but without inositol phosphate production. This Ca2+ rise was completely inhibited by 100 microM ryanodine. Adrenaline (causing activation of both alpha- and beta-adrenergic receptors) induces a Ca2+ release with inositol phosphate synthesis identical to that occurring in the beta-adrenergic response. Thus, the signalling pathway for alpha-adrenergic stimulation occurs via a path different from that which releases Ca2+ via muscarinic cholinergic and beta-adrenergic stimulation. In permeabilized lacrimal acinar cells cyclic adenosine 5'-diphosphoribose (cADP-ribose) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] cause release of Ca2+ from intracellular stores. The Ca2+ release evoked by cADP-ribose, but not by Ins(1,4,5)P3, was abolished by 100 microM ryanodine, implicating a possible involvement of cADP-ribose in phenylephrine-induced Ca2+ signalling. When the intracellular free Ca2+ concentration ([Ca2+]i) is raised by application of ionomycin, inositol phosphates are synthesized with a half-maximal effect seen at 425 nM. In contrast, loading cells with the Ca2+ chelator 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) reduced the adrenaline-induced inositol phosphate synthesis by 27%. The stimulation-induced rise in [Ca2+]i, therefore, appears to cause further synthesis of inositol phosphates, thereby amplifying the receptor-mediated response.

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@article{Gromada1995TheRO, title={The release of intracellular Ca2+ in lacrimal acinar cells by alpha-, beta-adrenergic and muscarinic cholinergic stimulation: the roles of inositol triphosphate and cyclic ADP-ribose.}, author={Jesper Gromada and Tino Dyhring J\orgensen and Steen Dissing}, journal={Pflugers Archiv : European journal of physiology}, year={1995}, volume={429 6}, pages={751-61} }