We have isolated a cDNA clone from the nematode Caenorhabditis elegans that encodes a protein of greatest sequence similarity to muscarinic acetylcholine receptors. This gene codes for a polypeptide of 682 amino acids containing seven putative transmembrane domains. The amino acid identities, excluding a highly variable middle portion of the third intracellular loop, to the human m1-m5 receptor...

Muscarinic M2 receptor antagonists with high subtype selectivity (M2/M1) will decrease the toxicity in central nervous system in treatment of AD. The exploration of quantitative structure-selectivity relationship (QSSR) to muscarinic M2 receptor antagonists will provide design information for drug with fewer side effects. In this paper, CoMFA models of pK(i)(M1), pK(i)(M2) and p[K(i)(M2)/K(i)(M...

In the in vivo experiments on anaesthetized sheep, it was presently examined whether muscarinic receptor antagonists with diverse selectivity affect the release of VIP in response to electrical stimulation of the parasympathetic chorda tympanic nerve differently, and if the changes in the release could be associated to altered secretory and vasodilator responses. The location of the muscarinic ...

We investigated the subtypes of the muscarinic receptor mediating short-term heterologous desensitization in the isolated ileum. Treatment of the ileum from C57BL/6 mice with acetylcholine (30 microM) for 20 min caused a subsequent decrease in contractile sensitivity to both prostaglandin F2alpha (PGF2alpha) and the muscarinic agonist, oxotremorine-M. This subsensitivity was characterized by 7-...

Based on the existence of choline acetyltransferase and acetylcholine in human placenta, we have investigated the presence of muscarinic acetylcholine receptors in brush-border and basal plasma membranes from human term placenta. Radioligand binding assay, using [3H]N-methyl-scopolamine as tracer, showed the existence of acetylcholine muscarinic receptors in brush-border (Kd 0.28 +/- 0.04 nM; B...

Xanomeline is a functionally selective M1/M4 muscarinic acetylcholine receptor agonist. We have previously identified a novel mode of interaction of this ligand with the muscarinic M1 receptor that involves persistent binding and activation of the receptor after extensive washout. In the present study, we tested the hypothesis that xanomeline also binds in a wash-resistant manner to muscarinic ...

pontine reticular formation of the rat is capable of inducing long-lasting increases in REM sleep (Bourgin et al., 1995; Marks and Birabil, 1998). These effects are blocked by a previous injection of the non-selective, muscarinic antagonist atropine supporting mediation by muscarinic receptors (Bourgin et al., 1995; Marks and Birabil, 1998). Five different muscarinic receptor subtypes have been...

Expression of KCNQ2/3 (Kv7.2 and -7.3) heteromers underlies the neuronal M current, a current that is suppressed by activation of a variety of receptors that couple to the hydrolysis of phosphatidylinositol 4,5-bisphosphate. Expression of Kv7.2/7.3 channels in human embryonic kidney (HEK) 293 cells produced a noninactivating potassium current characteristic of M current. Muscarinic receptors en...

Imidafenacin is a potent and selective antagonist of M1 and M3 muscarinic receptors that is safe, efficacious, and well tolerated for controlling the symptoms of overactive bladder (OAB). However, the precise mechanisms responsible for the bladder-selective pharmacological effects of this agent remain unclear. The in vivo pharmacologic effects of imidafenacin result from receptor occupancy. The...

Large volumes of saliva are generated by transepithelial Cl(-) movement during parasympathetic muscarinic receptor stimulation. To gain further insight into a major Cl(-) uptake mechanism involved in this process, we have characterized the anion exchanger (AE) activity in mouse serous parotid and mucous sublingual salivary gland acinar cells. The AE activity in acinar cells was Na(+) independen...