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...

Forebrain muscarinic acetylcholine (ACh) receptors (mAChRs; M1-M5) are predicted to play important roles in many fundamental central functions, including higher cognitive processes and modulation of extrapyramidal motor activity. Synaptic ACh levels are known to be regulated by the activity of presynaptic muscarinic autoreceptors mediating inhibition of ACh release. Primarily because of the use...

It is demonstrated that acetylcholine released from cholinergic interneurons modulates the excitability of neostriatal projection neurons. Physostigmine and neostigmine increase input resistance (RN) and enhance evoked discharge of spiny projection neurons in a manner similar to muscarine. Muscarinic RN increase occurs in the whole subthreshold voltage range (-100 to -45 mV), remains in the pre...

Muscarinic acetylcholine receptors exert slow and prolonged synaptic effects in both vertebrate and invertebrate nervous systems. Through activation of G proteins, they typically decrease intracellular cAMP levels by inhibition of adenylate cyclase or stimulate phospholipase C and the turnover of inositol phosphates. In insects, muscarinic receptors have been credited with two main functions: i...

To investigate whether a particular receptor subtype can be coupled to multiple effector systems, recombinant M2 muscarinic receptors were expressed in cells lacking endogenous receptor. The muscarinic agonist carbachol both inhibited adenylyl cyclase and stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was significantly less efficient and more dependent on...

The Morris water maze (MWM) is regarded as one of the most popular tests for detecting spatial memory in rodents. Long-term potentiation and cGMP synthesis seem to be among crucial factors involved this type learning. Muscarinic (M1, M4, M5 receptors) metabotropic glutamate (mGlu) receptors are important targets search antipsychotic drugs with potency treat cognitive disabilities associated dis...

PURPOSE To determine the functional role of M(3) and M(5) muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice. METHODS Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M(3) and M(5) receptors, ophthalmic arteries from mice deficient in either subtype (M3R(-/-), M5R(-...