This study characterized the functional effects of a novel gastroprokinetic agent, N-[2-(diisopropylamino)ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-1, 3-thiazole-4-carboxyamide monohydrochloride trihydrate (Z338), on the muscarinic M1, M2, and M3 receptors expressed in Xenopus oocytes using the two-electrode voltage clamp method. Z-338 did not produce by itself any currents in oocytes ex...

It has been generally accepted that, of the five subtypes of muscarinic receptors (M(1)-M(5)), only the M(2) subtype is expressed in mammalian heart. This notion has recently been challenged by a series of reports indicating that mRNAs for some or all non-M(2) subtypes are also present in mammalian heart, in parallel with the M(2) mRNA. However, the quantities of relevant mRNAs reported to be p...

We have used the chick embryonic heart to study the regulation of the muscarinic acetylcholine receptor in vivo. Sustained activation of the muscarinic receptor in vivo with the cholinergic agonist carbachol decreases muscarinic receptor number as much as 87% as measured by the specific binding of the potent muscarinic receptor in antagonist [3H]quinuclidinyl benzilate. The decrease in receptor...

Degeneration of the cholinergic system is considered to be the underlying pathology that results in the cognitive deficit in Alzheimer's disease. This pathology is thought to be linked to a loss of signaling through the cholinergic M(1)-muscarinic receptor subtype. However, recent studies have cast doubt on whether this is the primary receptor mediating cholinergic-hippocampal learning and memo...

We studied the interaction of disopyramide, quinidine, and procainamide with cardiac muscarinic receptors. In electrophysiological experiments, the effects of disopyramide, quinidine, procainamide, and atropine were determined on spontaneously depolarizing guinea pig right atria (GPRA) both in the presence and absence of pharmacologically induced (physostigmine) cholinergic stimulation. All fou...

PURPOSE We evaluated the alterations of density, localization and subtype specificity of muscarinic receptors in experimentally-induced diabetic rat bladder. METHODS Five groups of rats were maintained for sixteen weeks 1) diabetic, 2) diabetic insulin-treated (insulin started 8 weeks after the onset of diabetes), 3) sucrose-fed diuretic, 4) sucrose-removed and 5) age matched controls. We use...

In brain stem slices from neonatal (postnatal days 0-4) CD-1 mice, muscarinic ACh receptors (MAChRs) increased rhythmic inspiratory-related and tonic hypoglossal nerve discharge and depolarized single hypoglossal motoneurons (HMs) via an inward current without changing input resistance. These responses were blocked by the MAChR antagonist 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAM...

Preincubation with receptor agonists or phorbol esters desensitized muscarinic-receptor-mediated [3H]cyclic GMP responses in mouse neuroblastoma N1E-115 cells. However, desensitization mediated by phorbol esters was heterologous, whereas that effected by receptor agonist was specific towards the muscarinic receptors. In addition, there was no loss of cell surface muscarinic receptors, as measur...

Prior studies have suggested that heart expresses only the M2 isoform of the muscarinic receptor (Peralta, E.G., Ashkenazi, A., Winslow, J.W., Smith, D.H., Ramachandran, J., and Capon, D.J. (1987) EMBO J. 6, 3923-3929). Tietje and Nathanson (Tietje, K.M., and Nathanson, N. M. (1991) J. Biol. Chem. 266, 17382-17387) have recently demonstrated that the chick heart may be unique since it expresses...

Schizophrenia is a severe psychiatric illness with a lifetime prevalence of ˜1% that imposes a huge toll on patients, their families and public health services worldwide. Delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior and negative symptoms constitute the core symptoms of schizophrenia. Although the neurotransmitter dopamine plays a prominent role in t...