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.
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.
Gromada
J
J
Department of Medical Physiology, University of Copenhagen, Panum Institute, Denmark.
Jørgensen
T D
TD
Dissing
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D004533:Egtazic Acid; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007545:Isoproterenol; D000109:Acetylcholine; D002118:Calcium; D004837:Epinephrine