Isoproterenol potentiates alpha-adrenergic and muscarinic receptor-mediated Ca2+ response in rat parotid cells.
The effects of the cAMP pathway on the Ca2+ response elicited by phospholipase C-coupled receptor stimulations were studied in rat parotid cells. Although 1 microM isoproterenol (Iso) itself had no effect on the cytosolic Ca2+ concentration, the pretreatment with Iso potentiated Ca2+ responses evoked by phenylephrine. The potentiating effect of Iso was attributed to a shifting of the concentration-response curves of phenylephrine to the left and an increase in the maximal response. Half-maximal potentiation occurred at 3 nM Iso. Iso also potentiated the Ca2+ response elicited by carbachol. The potentiating effect of Iso was mimicked by forskolin (10 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (2 mM) and was blocked by 10 microM H-89. Iso potentiated the phenylephrine-induced Ca2+ response in the absence of extracellular Ca2+, but Iso did not increase the inositol trisphosphate (IP3) production induced by phenylephrine. These results suggest that the potentiation of the Ca2+ response can be attributed to a sensitization of IP3 receptors by cAMP-dependent protein kinase.
Tanimura
A
A
Department of Dental Pharmacology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. tanimura@hoku-iryo-u.ac.jp
Nezu
A
A
Tojyo
Y
Y
Matsumoto
Y
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004357:Drug Synergism; D007295:Inositol Phosphates / Q000096:biosynthesis; D007425:Intracellular Membranes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009994:Osmolar Concentration; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D010656:Phenylephrine; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D002118:Calcium