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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Responses to the nondepolarizing muscle relaxant, metocurine, were studied in eight hemiplegic and eight unmatched patients with normal motor strength during the general anesthetic given for various neurosurgical operations. Metocurine, 0.3 mg/kg, was administered intravenously, and indirectly evoked thumb twitch tensions were measured on both sides in the hemiplegic patients, and on one side in the normal patients. Arterial blood samples were obtained as twitch tension was recovering, and serum metocurine concentrations were determined using a specific radioimmunoassay. Percentage of paralysis was plotted as a function of log [metocurine] and the data were compared by analysis of covariance. For the normal motor strength patients, r = 0.84; for the unaffected arm of the hemiplegic patients, r = 0.69; and for the affected arm of the hemiplegic patients, r = 0.86, all significant at P less than 0.001. The mean plasma metocurine concentrations at 20, 25, 50, 75, and 80% paralysis were significantly different for all groups (P less than 0.001). The regression lines, in turn, did not overlap and were significantly different, each from the other (P less than 0.005). We were, however, unable to detect any significant deviation from parallelism among the three regression lines. We also measured time to 50% return of single twitch height for each data group as follows (mean +/- SEM: for NMS patients, 242 +/- 73 min; for the unaffected arm of hemiplegic patients, 116 +/- 60 min; and for the affected arm of hemiplegic patients, 59 +/- 36 min. By ANOVA and the Bonferroni test, each value was different from the other at P less than or equal to 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased sensitivity to metocurine in patients with upper motoneuron disease. 316 Feb 62

Radioligand receptor binding and autoradiography were used to characterize and localize the muscarinic cholinergic receptor in human benign prostatic hyperplastic tissue. These methods have not been used previously to investigate the autonomic innervation of the human prostate. The binding of [3H]N-methylscopolamine ([3H]NMS), a muscarinic cholinergic antagonist, to homogenates of human prostate was saturable and of high affinity. The equilibrium dissociation constant, (Kd), for [3H]NMS binding to human prostate homogenates was 0.10 +/- 0.03 nM (mean +/- SEM). The values of the Kd's for [3H]NMS binding to prostates of man (0.10 nM), dog (0.20 nM), pig (0.11 nM), rat (0.07 nM) and rabbit (0.15 nM) were similar, suggesting homogeneity of muscarinic cholinergic receptors in varying species. The mean density, B(max), of muscarinic cholinergic receptors identified in the human prostate was 2.1 fmol./mg. prostate wet weight. The relative density of receptors in the human prostates were similar in the homogenates and slide-mounted tissue sections. The pharmacology of NMS binding sites on slide-mounted tissue sections was evaluated by competitive binding experiments using [3H]NMS and atropine. The IC50 corrected of atropine on slide-mounted tissue sections (0.42 nM) was similar to values obtained in prostate homogenates (1.16 nM). Autoradiography on slide-mounted tissue sections demonstrated that the muscarinic cholinergic receptors were localized to the epithelium of the prostate. The ratio of specific NMS binding in the epithelial and stromal components of the prostate, expressed as autoradiographic grains/unit area and autoradiographic grains/cell, was 71:1 and 33:1 respectively. Because prostatic secretion is dramatically enhanced by muscarinic cholinergic agonists, localization of muscarinic cholinergic receptors to the epithelium is consistent with the neuropharmacology of prostatic secretion. These studies have provided basic insight into the neuropharmacology of the prostate. Future studies will be necessary to characterize and localize other neurotransmitters in the human prostate in order to further enhance our understanding of prostatic function.
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PMID:Characterization and localization of the muscarinic cholinergic receptor in human prostatic tissue. 620 69

Atropine and glycopyrronium are frequently used for premedication to reduce oral and respiratory secretions and prevent bradycardia. Glycopyrronium is said to have similar antisialagogue effects, but is less likely to cause significant tachycardia than atropine. Different antimuscarinic receptor selectivity patterns could explain the differences. The aim of this investigation was to determine the possible selectivity of glycopyrronium for M2 and M3 muscarinic receptor subtypes. Muscarinic receptor subtypes in Wistar rat ventricle and submandibular gland homogenates were characterized with [3H]-N-methylscopolamine ([3H]-NMS) by ligand binding studies. Inhibition of [3H]-NMS binding by non-labelled compounds showed the following order: in rat ventricle: glycopyrronium > atropine >> otenzepad > hexahydrosiladiphenidol (HHSiD) > pirenzepine; in rat submandibular gland: glycopyrronium > atropine >> HHSiD >> pirenzepine > otenzepad. These were similar to the expected order of frequency of M2 and M3 subtypes, respectively. Glycopyrronium showed similarly high affinities for both M2 (Ki = 1.889 (SEM 0.049) nmol litre-1) and M3 (Ki = 1.686 (0.184) nmol litre-1) subtypes. Glycopyrronium bound to a homogeneous population of binding sites in both tissues and showed no selectivity for M2 or M3 muscarinic receptor subtypes.
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PMID:Atropine and glycopyrronium show similar binding patterns to M2 (cardiac) and M3 (submandibular gland) muscarinic receptor subtypes in the rat. 777 19

Among the five subtypes of muscarinic acetylcholine receptors, the sensitivity towards allosteric modulation is generally higher in M2 and M4 receptors that preferentially couple to inhibitory G-proteins of the Gi/o type than in M1, M3, and M5 that preferentially couple to stimulatory G-proteins such as Gq/11. We aimed to check whether the high allosteric sensitivity of the M2 receptor compared to M3 is related to the differential G-protein coupling preference. As the third intracellular loop (i3) is known to be the major determinant in receptor G-protein coupling specificity, we used wild-type M2 and M3 receptors and the related chimeric constructs with exchanged i3-loops, i.e., M2 containing M3-i3 (M2/M3-i3) and M3 containing M2-i3 (M3/M2-i3). The allosteric effect of the archetypal modulator gallamine on the dissociation and the equilibrium binding of [3H]N-methylscopolamine ([3H]NMS) was measured in membranes of mouse A9L cells stably expressing the wild-type and the chimeric receptors (4 mM Na2HPO4, 1 mM KH2PO4, pH 7.4, 23 degrees C). The dissociation of [3H]NMS was monophasic under all conditions studied. Control values of t 1/2 were (means +/- SEM, n = 4-7): M2: 3.8 +/- 0.2 min, M2/M3-i3: 4.8 +/- 0.3 min, M3:43.3 +/- 4.2 min, M3/M2-i3: 41.1 +/- 3.6 min. At M2 receptors, 0.2 microM gallamine allosterically reduced the apparent rate constant of dissociation k-1 to 51 +/- 5% of the control value (n = 5). At M2/M3-i3 the allosteric potency of gallamine was not significantly changed (0.2 microM gallamine --> k-1 = 61 +/- 4%, n = 7). At M3, a 20-fold higher concentration was required for an equieffective allosteric action (10 microM gallamine --> k-1 = 51 +/- 5%, n = 5). The potency of gallamine at M3/M2-i3 was not increased compared with M3 receptors (10 microM gallamine --> k-1 = 73 +/- 2%, n = 4) but even significantly diminished. [3H]NMS equilibrium binding experiments revealed that neither the binding constants of gallamine at free receptor subtypes (pKA,M2: 7.57 +/- 0.04, n = 4; pKA,M3: 5.56 +/- 0.13, n = 3) nor the factors of negative cooperativity with [3H]NMS (alphaM2 = 31 +/- 1, alphaM3 = 3 +/- 0.4) were affected by the exchanged i3-loops (pKA,M2/M3-i3: 7.65 +/- 0.03, pKA,M3/M2-i2: 5.35 +/- 0.24, alphaM2/M3-i3= 30 +/- 2, alphaM3/M2-i2 = 3 +/- 0.7). In conclusion, the different sensitivities of M2 and M3 receptors towards allosteric modulation by gallamine are not related to the G-protein coupling specificity of the receptors.
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PMID:Muscarinic allosteric modulation: M2/M3 subtype selectivity of gallamine is independent of G-protein coupling specificity. 1153 57