Up to date, there are four pharmacologically characterized subtypes of muscarinic receptors (M1, M2, M3 and M4). In our study we have investigated muscarinic receptor subtypes in smooth muscle layers of human stomach. Isolated preparations of longitudinal and circular muscle layers from human stomach were used. Acetylcholine, bethanechol, carbachol, pilocarpine and AHR -602 produced concen...

Although the heart is considered a relatively pure source of m2 muscarinic receptors, the possible expression of other muscarinic receptor genes at discrete sites within the myocardium or by intrinsic cardiac ganglia had not been evaluated. Accordingly, the present study used in situ hybridization histochemistry with "S-labeled oligonucleotide probes to address this issue. Initial experiments d...

The molecular mechanisms through which muscarinic receptors are activated upon binding of the neurotransmitter acetylcholine (ACh) are still poorly understood. Classical structure-function relationship studies have previously established that the ACh ester moiety plays a key role in muscarinic receptor recognition and activation. Consistent with this notion, all recently proposed three-dimensio...

One component of muscarinic receptor inhibition of the function of cardiac ventricles is mediated by the inhibition of activated adenylate cyclase activity in sarcolemma. We have shown previously that muscarinic agonists inhibit GTP- but not Gpp(NH)p-activated adenylate cyclase activity, and various studies in other tissues indicate that nonhydrolyzable GTP analogues prevent inactivation of the...

OBJECTIVE Postmortem studies have implicated the central muscarinic acetylcholine system in schizophrenia. However, central muscarinic receptor availability has not previously been studied in vivo. Using [I-123]iodoquinuclidinyl benzilate ([(123)I]IQNB) single photon emission computed tomography (SPECT), the authors sought to compare the muscarinic receptor availability in vivo in unmedicated p...

This study examined cross talk between phospholipase C-coupled muscarinic M(3) and bradykinin B(2) receptors coexpressed in Chinese hamster ovary (CHO) cells. Agonists of either receptor enhanced phosphoinositide signaling (which rapidly desensitized) and caused protein kinase C (PKC)-independent, homologous receptor phosphorylation. Muscarinic M(3) but not bradykinin B(2) receptors were also p...

Epibatidine, a neurotoxin isolated from the skin of Epipedobates tricolor, is an efficacious antinociceptive agent with a potency 200 times that of morphine. The toxicity of epibatidine, because of its nonspecificity for both peripheral and central nicotinic receptors, precludes its development as an analgesic. During the synthesis of epibatidine analogs we developed potent antinociceptive agen...

Activation of muscarinic cholinergic receptors on pyramidal cells of the cerebral cortex induces the appearance of a slow afterdepolarization that can sustain autonomous spiking after a brief excitatory stimulus. Accordingly, this phenomenon has been hypothesized to allow for the transient storage of memory traces in neuronal networks. Here we investigated the molecular basis underlying the mus...

Prepulse inhibition (PPI) of the acoustic startle reflex is a sensorimotor gating process known to be deficient in a number of neurologic and psychiatric conditions, including schizophrenia. Multiple lines of evidence have indicated that the dopaminergic and muscarinic cholinergic systems play an important role in modulating PPI. Moreover, interactions between the dopaminergic and muscarinic ch...

The overproduction of β-amyloid (Aβ) fragments in transgenic APPswe/PS1dE9 mice results in formation of amyloid deposits in the cerebral cortex and hippocampus starting around four months of age and leading to cognitive impairment much later. We have previously found an age and transgene-dependent weakening of muscarinic receptor-mediated transmission that was not present in young (6-10-week-ol...