MUSCARINIC RECEPTOR - MEDIATED PHOSPHOINOSITIDE HYDROLYSIS IN RAT BRAIN

Year 1999, Volume: 12 Issue: 1, 25 - 28, 03.12.2016

Hülya Cabadak Beki Kan

Abstract

Objective: Activation of cholinergic muscarinic receptors leads to activation of membrane - bound phospholipase C, leading to generation of IP3 and diacylglycérol, The present study aimed at measuring muscarinic receptor-mediated phosphoinositide breakdown in three different regions of rat brain.
Methods: Cortical, hippocampal and striatal slices labeled with [3H] myo-inositol were incubated with muscarinic agonist carbachol (Cch) and LiCI. Reaction was terminated by the addition of chloroform/methanol and labeled inositol phosphates were extracted from tissue. Individual [3H]- inositol phosphates were separated using anion exchange chromatography.
Results: Cch caused a rise in IP, formation, where the increase over basal in the cortex, hippocampus and striatum were 98%, 73% and 45%, respectively.
Conclusion: Phosphoinositide turnover was
stimulated by carbachol in all brain structures studied, with the most pronounced effects observed in the cortex and hippocampus.
Key Words: Muscarinic receptors, inositol
phosphates, carbachol, rat brain

References

• Waelbroeck M, Tastenoy M, Camus J, Christophe J. binding of selective antagonists to four muscarinic receptors (Mt to M4) in rat forebrain. Mol. Pharmacol. 1990;38:267-273.
• Bonner Tl, Buckley ilJ, Young AC and Brann MR. Identification of a family of muscarinic acetylcholine receptor genes. Science 1987;237:527-532.
• Bonner Tl, Young AC, Brann MR and Buckley IYJ. Cloning and expression of the human and rat M5 muscarinic acetylcholine receptor genes, neuron 1988;1:403-410.
• Peralta EG, Ashkenazi A, Winslow JW, Smith DU, Ramachandran J and Capon DJ. Distinct primary structures, ligand binding properties and tissue- spicific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987:6:3923- 3929.
• Buckley MJ, Bonner Tl and Brann MR. Localization of a familiy of muscarinic receptor mRMAs in rat brain. J. Meurosci. 1988:8:4646-4652.
• Yasuda RP, Ciesla W, Flores LR, Wall SJ, Li M, Satkus 5/1, Weisstein JS, Spagnola BV, Wolfe BB. Development of antisera specific for M4 and M5 muscarinic cholinergic receptors: Distribution of M4 and M5 receptors in rat brain. Mol. Pharmacol. 1992;43:149-157.
• Brann MR, Buckley nj, Bonner Tl. The striatum and cerebral cortex express different muscarinic receptor mRMAs. FEBS Lett. 1988;230:90-94.
• Mei L, Roeske WR, Yamamura til. Molecular pharmacology of muscarinic receptors heterogeneity. Life Sci. 1989;45:1831-1851.
• Dorje F, Levey Al and Brann MR. Immunological detection of muscarinic receptor subtype proteins (MrM5) in rabbit peripheral tissues. Mol. Pharmacol. 1991;40:459-462.
• tlersch SM, Gutekunst CA, Rees HD, Heilman CJ and Levey Al. Distrubition of M ¡-M4 muscarinic
• Marmara Medical Journal Volume 12 No: 1 January 1999
• receptor proteins in the rat striatum: Light and electron microscopic immunocytochemistry using subtype specific antisera. J. rieurosci. 1994;14:3351-3363.
• Peralta EG, Ashkenazi A, Winslow JW, Ramachandran J and Capon DJ, Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes. nature 1988;334:434-437.
• Bonner Tl. new subtypes of muscarinic acetylcholine receptors. Trends. Pharmacol. Sci. 1989;(Suppl.):l 1-15.
• Parker EM, Kameyama K, Fligashijima T and Ross EM. Reconstitutively active G-protein-coupled receptors puriPied from baculovirus-infected insect cells. J. Biol. Chem. 1991;266:519-527.
• Gonzales RA, Crews FT. Characterization of the cholinergic stimulation of phosphoinositide hydrolysis in rat brain slices. J. Meurosci. 1984;4:3120-3127.
• Brown ED, Kendall DA, Mahorski SR. Inositol phospholipid hydrolysis in rat cerebral cortical
• slices. I. Receptor characterization. J. neurochem. 1984;42:1379-1387.
• Fisher KS, Fiqueiredo JC, Bartus RT. Differential stimulation of inositol phospholipid turnover in brain by analogs of oxotremorine. J. neurochem. 1984;43:l 171-1 179.
• Fisher KS, Bartus RT. Regional differences in the coupling of muscarinic receptors to inositol phospholipid hydrolysis in guinea pig brain. J. neurochem 1985;45:1085-1095.
• Berridge MJ. Rapid accumulation of inositol triphosphate reveals that agonists hydrolyse phosphoinositides instead of phosphatidylinositol. Biochem. J. 1983;212:849-858.
• Lowry Oft, Rosebrough nJ, Farr AL and Randall RJ. Protein measurement with the folin phenol reagent.
• J. Biol. Chem. 1951;193:265-275.
• Tonnaer JADM, Cheung CL, DeBoer T. cGMP Formation and phosphoinositide turnover in rat brain slices are mediated by pharmacologically distinct muscarinic acetylcholine re