Evidence that isoproterenol-induced Ca2(+)-mobilization in rat parotid acinar cells is not mediated by activation of beta-adrenoceptors.
The effects of isoproterenol (ISO), a beta-adrenoceptor agonist, on cytosolic free Ca2+ ([Ca2+]i) in rat parotid acinar cells were examined using the fluorescent Ca2(+)-indicator fura-2. At concentrations up to 1 mM, ISO caused a rapid increase in [Ca2+]i in a dose-dependent manner, while addition of 1 microM ISO, which evokes the maximum amylase secretion, had only a slight effect on [Ca2+]i. There was no such increase in [Ca2+]i with the addition (2 mM) of 8-bromo-cyclic AMP, a permeant cyclic AMP analogue. The alpha-adrenoceptor antagonist phentolamine blocked the ISO-induced [Ca2+]i increase better than the beta-adrenoceptor antagonist, propranol, and the muscarinic receptor antagonist, atropine. The IC50 value (the concentration which reduces the ISO-induced increase in [Ca2+]i by 50%) of phentolamine was estimated to be 7.6 nM, for propranolol 13.2 microM and for atropine 3.5 microM. The difference in potency between the three antagonists was similar to the difference in blocking the [Ca2+]i increase induced by phenylephrine, an alpha-adrenoceptor agonist. These results suggest that the Ca2(+)-mobilization in response to high concentrations of ISO results from an activation of alpha-adrenoceptors rather than beta-adrenoceptors.
Tanimura
A
A
Department of Dental Pharmacology, School of Denistry, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Matsumoto
Y
Y
Tojyo
Y
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D018727:Muscarinic Antagonists; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D001285:Atropine; D002217:Carbachol; D011433:Propranolol; D007545:Isoproterenol; D002118:Calcium; D010646:Phentolamine