Inhibition of muscarinic stimulated phosphoinositide hydrolysis in the rat parotid gland by cAMP.
The ability of agents that increase or mimic cAMP to affect muscarinic receptor mediated phosphoinositide hydrolysis was investigated in the rat parotid gland. Forskolin (10 microM) and isoproterenol (10 microM) elevated cAMP in the parotid gland by 2-fold and 7-fold, respectively, and these agents also inhibited oxotremorine-M (3 microM) mediated phosphoinositide hydrolysis by 14% and 26%, respectively. Forskolin (1, 4.3, 18, and 75 microM) increased cAMP accumulation and inhibited PIP2 hydrolysis in a concentration-dependent manner. Forskolin (75 micrometers) shifted the concentration-response curve for the full agonist oxotremorine-M rightward by 4.2-fold. Pre-treatment with the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) reduced the maximum effect of oxotremorine-M by 31%. The inhibitory effect of isoproterenol and forskolin on muscarinic receptor-mediated phosphoinositide hydrolysis was unaffected by the removal of extracellular Ca2+. Moreover, isoproterenol and forskolin dampened sodium fluoride and oxotremorine-M mediated phosphoinositide hydrolysis to the same extent suggesting that the inhibitory effect of cAMP is downstream from the muscarinic receptor.
Gerstin
E H
EH
Department of Pharmacology, College of Medicine, University of California, Irvine, 92717 USA.
Ehlert
F J
FJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D006868:Hydrolysis; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*; D012969:Sodium Fluoride / Q000494:pharmacology; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010716:Phosphatidylinositols; D010726:Phosphodiesterase Inhibitors; D011976:Receptors, Muscarinic; D005576:Colforsin; D010095:Oxotremorine; D012969:Sodium Fluoride; D000242:Cyclic AMP; D015232:Dinoprostone; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine