Beta-adrenergic stimulation and cAMP mobilize Ca2+ from an IP3-insensitive pool in rat submandibular granular ducts
Dehaye, J.P.; Valdez, I.H.; Turner, R.J.
American Journal of Physiology 265(5 Pt 1): C1356-C1362
1993
ISSN/ISBN: 0002-9513 PMID: 7694495 Document Number: 408970
The beta-adrenergic agonist isoproterenol induced an increase in intracellular calcium concentration ((Ca-2+)-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 not blocked by protein kinase inhibitors. The response of (Ca-2+)-i to isoproterenol was sustained in Ca-2+-replete medium but transient in Ca-2+-free medium, indicating the involvement of both Ca-2+ 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 (Ca-2+)-i after the carbachol-induced depletion of inositol 1,4,5-trisphosphate (IP-3)-sensitive calcium stores. We conclude that isoproterenol, acting through cAMP, releases Ca-2+ from an IP-3-insensitive intracellular store in salivary granular ducts.