M3 subtype muscarinic receptors (CHRM3) are over-expressed in colon cancer. In this study, we used Apc(min/+) mice to identify the role of Chrm3 expression in a genetic model of intestinal neoplasia, explored the role of Chrm3 in intestinal mucosal development and determined the translational potential of inhibiting muscarinic receptor activation. We generated Chrm3-deficient Apc(min/+) mice an...

The muscarinic receptors in a B82 cell line which were transfected with the rat m1 muscarinic receptor gene (cTB10 cells) were studied by using radioligand binding assays. Their possible coupling to the hydrolysis of inositol lipids and cyclic AMP formation were also investigated. [(-)-[3H]Quinuclidinyl benzilate [(-)-[3H]QNB] binding to the intact cTB10 cells was saturable and displaceable by ...

These experiments tested whether nucleus accumbens muscarinic or nicotinic acetylcholine receptor activation is required for rats to learn to lever press for sucrose. Muscarinic blockade with scopolamine (1.0 microg/side or 10.0 microg/side), but not nicotinic antagonism with mecamylamine (10.0 microg/side), inhibited learning and performance when applied to the core or shell. Further experimen...

The influence of bilateral electrolytic lesions of different parts of the septum on muscarinic receptor binding in the hippocampus was studied within 14-21 days after operation. The effect of total septal lesion upon receptor binding was also investigated separately in the dorsal and ventral hippocampus and in five consecutive hippocampal parts along the septotemporal axis of the structure. The...

Objective: Activation of cholinergic muscarinic receptors leads to activation of membrane bound phospholipase C, leading to generation of IP3 and diacylglycérol, The present study aimed at measuring muscarinic receptor-mediated phosphoinositide breakdown in three different regions of rat brain. Methods: Cortical, hippocampal and striatal slices labeled with [3H] myo-inositol were incubated with...

The effects of various substrates on the binding of agonists to muscarinic receptors were studied in the rat hypothalamus and adenohypophysis by competition experiments using the highly specific tritiated muscarinic antagonist N-methyl-4-piperidyl benzilate. It was found that agonist binding properties were affected only by the steroid sex hormones (beta-estradiol and progesterone), both of whi...

Therapeutic repair of myelin disorders may be limited by the relatively slow rate of human oligodendrocyte differentiation. To identify appropriate pharmacological targets with which to accelerate differentiation of human oligodendrocyte progenitors (hOPCs) directly, we used CD140a/O4-based FACS of human forebrain and microarray to hOPC-specific receptors. Among these, we identified CHRM3, a M3...

The M2 muscarinic acetylcholine receptor is a G-protein coupled receptor that undergoes agonist-induced internalization through an unidentified pathway that exhibits an atypical dependence on dynamin function in HEK293 cells. In this report we utilized several independent approaches to reveal that the internalization of the M2 muscarinic acetylcholine receptor did not utilize clathrin-coated pi...

AC2 (adenylate cyclase 2) is stimulated by activation of Gq-coupled muscarinic receptors through PKC (protein kinase C) to generate localized cAMP in HEK (human embryonic kidney)-293 cells. In the present study, we utilized a sensitive live-cell imaging technique to unravel the proteins that play essential roles in a Gq-coupled muscarinic receptor-mediated cAMP signalling complex. We reveal tha...