Neuropeptide modulation of muscarinic receptors and function in cerebral cortex of young and senescent rats |
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Affiliation: | 1. Water, Energy and Environmental Engineering Research Unit, Faculty of Technology, P.O. Box 4300, FI-90014, University of Oulu, Finland;2. Northern Ostrobothnia Centre for Economic Development, Transport and the Environment, P.O. Box 86, FI-90101, Oulu, Finland;1. Alfred Hospital, Commercial Road, Melbourne 3004, Australia;2. Deakin University, School of Nursing & Midwifery, Locked Bag 2000, Geelong, 3220 |
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Abstract: | The possible influence of several neuropeptides on muscarinic receptor binding and function in fronto-parietal cortex of young and senescent Fischer 344 rats was examined. Low concentrations (100 nM) of cholecystokinin, neurotensin and vasoactive intestinal polypeptide (VIP), added in vitro, enhanced carbachol-stimulated phosphoinositide metabolism in cortical miniprisms from both young and senescent rats, while somatostatin was ineffective. Interestingly, the VIP receptor antagonist [d-parachloro-Phe6, Leu17]VIP shifted the dose-response curve for carbachol significantly to the right, indicating inhibition of phosphoinositide hydrolysis. No direct actions of neuropeptides on the number or affinity of [3H]-quinuclidinyl benzilate binding sites nor on agonist conformation states of the muscarinic receptor were noted in cortex from young animals. The neuropeptide modulation of phosphoinositide metabolism was selective for muscarinic systems, as norepinephrine-stimulated phosphoinositide hydrolysis was not altered. Pretreatment with hemicholinium-3, an inhibitor of high-affinity choline uptake, did not prevent the neuropeptide effects, indicating the interaction was probably postsynaptic. It is possible that pharmacologic manipulation of peptidergic processes could improve cholinergic neurotransmission in brain. |
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