European Journal of PharmacoioD: 178 (1990) 91-96 Elsevier 91 F.JP 51225 Muscarinic suppression of the evoked N-wave by oxotreraofine-M recorded in the guinea-pig o|factory cortex s|ice Giacinto Bagetta i and Andrew Constant/ Department of Pharmacology, The School of Pharmacy, 29/39 Brunswick Square. London WCL~f lAX, U.K. Received 21 September1989,revised MS received12 December1989, accepted 2 January 1990 The effect of the muscarinic agonist oxotremorine-M has been studied on the surface-negative field potential (N-wave) evoked by orthodromic smnulation of the lateral olfactory tract in slices of guinea-pig olfactory cortex. Bath-application of oxotremorine-M (5-80/zM) or carbachol (10-300 #M) produced a reversible depression of the N-wave ampLmde without affecting the lateral olfactory tract compound action potential. Oxotremorine-M was - 5 times more potent than carbachol in this respect, and the effects of both agonists were competitively blocked by telenzepine (5-100 nM), a selective Mrreceptor antagonist. In contrast, methoctramine or AF-DX 116, two 'cardiose- lective' M2-receptor antagonists, had little or no blocking effect on the agonist responses. It is suggested that oxotremorine-M (like carbachol) inhibits the evoked field potential by activating presynaptic Ml-type muscarinic receptors in the olfactory cortex slice.. Oxotremorine-M; Olfactory cortex slice; Surface field potential (N-wave); Muscarinic receptors; (Guinea-pig) 1. |ntroducfion Radioligand binding and functional studies have demonstrated the existence of more than one type of muscafinic acetylcholine receptor (Hammer et al., 1980; Eglen and Whiting, 1986). High affin- ity binding sites for the competitive antagonist pirenzepine have been found in the cerebral cortex, superior cervical ganglia and enteric nervous sys- tem (M~-receptors), whereas low affinity sites (M2-receptors) predominate in certain brainstem regions and in atrial and ileal tissues. The regional bir~d'ng site heterogeneity in the brain has been supported by direct autoradiographic data (Warns- Permanent address: Institute of Pharmacology, Faculty of Medicine and Surgery, Catanzaro, University of Reggio Calabria, Italy. Correspondence to: A. Constanti, Department of Pharmacol- ogy, The School of Pharmacy, 29/39 Brunswick Square, London WC1N lAX, U.K. ley et al., 1984; Spencer et al., 1986). Despite the high density of M~-binding sites found in the cortex (Wamsley et al., 1984), their functional role in this ~ea of the brain remains unclear. It is well known that pyramidal neurones in layers lI-III of the pidform cortex receive an afferent synaptic input from terminals of the lateral olfactory tract (Haberly, 1983). Recently, using an extracellular recording technique, Wil- rams and Constanti (1988a,b) described the in- hibitory effects of muscarinic agonists on the surface-negative potential (N-wave) evoked by the stimulation of the lateral olfactory tract in guinea- pig olfactory cortex sli~s. It was proposed that these effects were mediated via presynaptic M~- receptor stimulation, since pirenzepine, but not gallamine (a cardioselective M2-receptor antago- nist), was able to antagonize them in a potent and competitive manner (Williams and Constanti, 1988b). Agonists such as muscadne, acetylcholine or carbachol were effective inhibitors of the field 0014-2999/90/$03.50 © 1990 ElsevierSciencePublishers B.V. (BiomedicalDivision)