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Involvement of endogenous nitric oxide signalling system in brain muscarinic acetylcholine receptor activation

Article

Authorship
Tania Borda ; GENARO, ANA MARIA ; Leonor Sterin-Borda ; Graciela Alicia Cremaschi
Date
1998
Publishing House and Editing Place
SPRINGER WIEN
Magazine
JOURNAL OF NEURAL TRANSMISSION. GENERAL SECTION., vol. 105 (pp. 193-204) SPRINGER WIEN
Summary Information provided by the agent in SIGEVA
Biochemical signalling events coupled to muscarinic cholinergic receptors (mAChR), specifically those related to nitric oxide (NO) production, were studied on rat cerebral frontal cortex. The mAChR agonist carbachol was found to exert a specific biphasic action on NO synthase (NOS) activity: low doses ranging between 10(-9) M to 10(-7) M lead to NOS activation while higher doses (>10(-6) M) inhibited enzymatic activity. Carbachol stimulatory action was blunted by agents that interfere with c... Biochemical signalling events coupled to muscarinic cholinergic receptors (mAChR), specifically those related to nitric oxide (NO) production, were studied on rat cerebral frontal cortex. The mAChR agonist carbachol was found to exert a specific biphasic action on NO synthase (NOS) activity: low doses ranging between 10(-9) M to 10(-7) M lead to NOS activation while higher doses (>10(-6) M) inhibited enzymatic activity. Carbachol stimulatory action was blunted by agents that interfere with calcium-calmodulin while a protein kinase (PKC) inhibitor, staurosporine was able to abrogate the inhibitory effect. Moreover, PKC activity showed maximum translocation to cerebral frontal cortex membranes with carbachol concentrations that inhibited NO production. Products from phosphoinosite (PI) hydrolysis are involved in these actions as carbachol was found to increase PI turnover in a dose dependent manner. These results would serve as an example of cross-talk between both enzymatic pathways.
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Key Words
Protein Kinase CNitric OxideCerebral Frontal CortexMuscarinic Acetylcholine ReceptorPhosphoinositide Turnover