Beta-adrenergic stimulation and cAMP mobilize Ca2+ from an IP3-insensitive pool in rat submandibular granular ducts.
The beta-adrenergic agonist isoproterenol induced an increase in intracellular calcium concentration ([Ca2+]i) in rat submandibular granular ducts that was blocked by beta-adrenergic but not by alpha-adrenergic or muscarinic antagonists. This effect was only partially inhibited by the selective beta 1- and beta 2-adrenergic antagonists atenolol and ICI-118,551, but was completely blocked by the combination of the two, suggesting the involvement of multiple (or atypical) beta-adrenergic receptor subtypes. The response to isoproterenol was mimicked by forskolin, 3-isobutyl-1-methylxanthine, and dibutyryl adenosine 3',5'-cyclic monophosphate, but it was blocked by protein kinase inhibitors. The response of [Ca2+]i to isoproterenol was sustained in Ca(2+)-replete replete medium but transient in Ca(2+)-free medium, indicating the involvement of both Ca2+ entry and release from intracellular stores. However, isoproterenol stimulation produced no increase in ductal inositol phosphate levels. In addition, isoproterenol was still able to increase [Ca2+]i after the carbachol-induced depletion of inositol 1,4,5-trisphosphate (IP3)-sensitive calcium stores. We conclude that isoproterenol, acting through cAMP, releases Ca2+ from an IP3-insensitive intracellular store in salivary granular ducts.
Dehaye
J P
JP
Department of General Biochemistry, Free University of Brussels, Belgium.
Valdez
I H
IH
Turner
R J
RJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D011412:Propanolamines; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D001262:Atenolol; D001285:Atropine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D011433:Propranolol; D000242:Cyclic AMP; D011493:Protein Kinase C; D019311:Staurosporine; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D011700:Putrescine; D004837:Epinephrine; D010646:Phentolamine