Differences in ligand binding and phosphoinositide turnover between M1 muscarinic receptor gene transfected cells and mouse and rat brain membranes

Wang, D.X.; Lerner-Marmarosh, Nicoll; Sheu, Shey‐Shing; Sharma, Virendra K.; Jou, Mei‐Jie; Abood, Leo G.

doi:10.1016/0091-3057(94)90441-3

Cited by 1 publication

(1 citation statement)

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“…In addition, despite its low affinity for brain muscarinic receptors in vitro . MCCh has been shown to promote a muscarinic‐mediated response in cell lines transfected with muscarinic receptors (Wang et al , 1994). Therefore, in keeping with these two latter studies, our results indicate that MCCh should be considered as a nonselective cholinoceptor agonist.…”

Section: Discussionmentioning

confidence: 99%

Activation of midbrain presumed dopaminergic neurones by muscarinic cholinergic receptors: an in vivo electrophysiological study in the rat

Gronier

Rasmussen

1998

British J Pharmacology

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1 Extracellular single-unit recording and iontophoresis were used to examine the e ects of di erent cholinoceptor agonists and antagonists on the ®ring rate and ®ring pattern of A9 and A10 presumed dopaminergic neurones in the anaesthetized rat. 2 Administration of low currents (1 ± 5 nA) of the selective muscarinic agonists oxotremorine M (Oxo M) and muscarine and of the non-selective muscarinic/nicotinic agonist carbamylcholine (CCh) produced a dose-dependent increase in ®ring rate in most of the A9 and A10 presumed dopaminergic neurones tested. Oxo M-induced activation could be completely blocked by iontophoretic application of the muscarinic antagonist butyl-scopolamine or systemic administration of the muscarinic antagonist scopolamine (300 mg kg 71 , i.v.). 3 Iontophoretic application of the selective nicotinic agonist methylcarbamylcholine (MCCh), but not nicotine, induced a consistent increase in ®ring rate. Surprisingly, the excitatory e ect of MCCh was signi®cantly reduced by the selective muscarinic antagonist scopolamine (300 mg kg 71 , i.v.), but not by the selective nicotinic antagonist mecamylamine (2.2 mg kg 71 , i.v.). Mecamylamine (3 mg kg 71 , i.v.) was also ine ective in reducing the CCh-induced activation of presumed dopamine neurones, suggesting that both CCh and MCCh increased the activity of dopamine neurones via an interaction with muscarinic receptors. 4 Iontophoretic application of the endogenous agonist acetylcholine (ACh) had no or little e ect on the ®ring activity of A10 presumed dopaminergic neurones. However, concomitant application of neostigmine, a potent cholinesterase inhibitor, with acetylcholine induced a substantial activation of these neurones. This activation consisted of two components; one, which was prevalent, was scopolamine (300 mg kg 71 , i.v.)-sensitive, and the other was mecamylamine (2 mg kg 71 , i.v.)-sensitive. 5 In addition to their e ect on ®ring activity, Oxo M, muscarine and concomitant neostigmine/ACh caused a signi®cant increase in burst ®ring of A10 neurones, but not of A9 neurones. 6 These data suggest that dopamine cells, both in the A9 and A10 regions, possess functional muscarinic receptors, the activation of which can increase their ®ring rate and, for A10 neurones, their amount of burst activity. These cholinoceptors would be able to in¯uence the activity of the midbrain dopamine system greatly and may play a role in, and/or be a therapeutic target for, brain disorders in which dopamine is involved (e.g., Parkinson's disease, drug addiction and schizophrenia).

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Section: Discussionmentioning

confidence: 99%