Studies of muscarinic receptor reserve linked to phosphoinositide hydrolysis in parotid gland and cerebral cortex.
Hydrolysis of inositol phospholipids caused by muscarinic agonists was studied in the guinea-pig parotid gland (PG) and cerebral cortex (CX). The present study describes the effect of two muscarinic agonists, carbachol and oxotremorine, on stimulation of phosphoinositide hydrolysis and on binding of [3H]NMS in the presence of the irreversible muscarinic antagonist benzilyl choline mustard (BCM). Carbachol and oxotremorine stimulated the formation of inositol phosphates in PG, pD2(Carb) = 5.3 +/- 0.1, pD2(Oxo) = 5.9 +/- 0.1 and in CX, pD2(Carb) = 4.3 +/- 0.2, pD2(Oxo) = 5.8 +/- 0.2. In the present study slices from both tissues have been exposed to 0.1 microM BCM for 2, 5 and 10 min. Treatment for 10 min caused a 75-85% reduction in specific [3H]N-methyl scopolamine ([3H]NMS) binding sites in both PG and CX. Following 2 min BCM treatment of PG a marked decrease in pD2 value of the carbachol-stimulated inositol phosphate formation was found. This effect was not found in CX. The results showed that a 30-40% reduction in binding sites shifted the carbachol concentration response curve to the right by one order of magnitude and reduced the oxotremorine-induced release of inositol phosphates by approximately 20%. In PG, the BCM-induced reduction of the carbachol-stimulated inositol phosphate formation was paralleled by the reduction in receptor binding sites. Similar treatment, but in CX, showed a lower reduction of the carbachol-stimulated inositol phosphate formation as compared to the reduction in receptor-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, University of Gothenburg, Sweden.
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D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D019832:N-Methylscopolamine; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000493:pharmacokinetics; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*; D012602:Scopolamine Derivatives / Q000494:pharmacology
D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D010890:Pirenzepine; C100238:benzilylcholine mustard; D010095:Oxotremorine; D002217:Carbachol; D002794:Choline; D019832:N-Methylscopolamine