Autoantibodies ; Calcium Channels ; Humans ; Myasthenia Gravis ; Receptors, Cholinergic/metabolism*

Acetylcholine ; pharmacology ; Adenocarcinoma ; metabolism ; Cell Line, Tumor ; Gastric Mucosa ; cytology ; drug effects ; metabolism ; Humans ; Receptors, Cholinergic ; metabolism ; Stomach Neoplasms ; metabolism

OBJECTIVETo investigate the changes of acetylcholine receptor (AChR) distribution at the neuromuscular junction (i.e. motor end-plate) following the free neurovascular muscle transfer.

METHODSAChR in the gracilis muscle of the Wistar rat following free neurovascular transfer were labeled by fluorescent alpha-bungarotoxin and radioiodinated alpha-bungarotoxin. Then confocal microscope and gamma-counting were estimated to ACHR, qualitatively and quantitatively.

RESULTSThe junctional AChR numbers decreased to a minimum at the fourth week postoperatively, whereas the extrajunctional receptor numbers increased. From the fifth week postoperatively, the number of junctional AChR's increased. Even at 30 weeks after transfer, the morphology of the neuromuscular junction failed to return to the preoperative style. The number of acetylcholine receptors at the reinnervated neuromuscular junction also remained lower than the control.

CONCLUSIONThe persistent weakness following free neurovascular muscle transfer may be attributed to these qualitative and quantitative changes at the neuromuscular junction.

Animals ; Female ; Motor Endplate ; metabolism ; Muscle, Skeletal ; transplantation ; Nerve Regeneration ; Postoperative Period ; Rats ; Rats, Wistar ; Receptors, Cholinergic ; metabolism

OBJECTIVETo explore the feature of the ACh-sensitive potassium current in guinea pig cochlear outer hair cells.

METHODSCochlear outer hair cells of guinea pigs (n=38) were isolated by collagenase type IV. Under the whole-cell patch mode, the ions nature and the pharmacological properties of the ACh-sensitive potassium current were investigated by applying the inhibitors of calcium-dependent potassium currents and the inhibitors of nicotinic ACh receptor.

RESULTSFollowing application of ACh, cochlear outer hair cells displayed a rapidly activating outward potassium current with a fast desensitized kinetic and a reversal (x +/- s) potential of (-67.3 +/- 8.2) mV (n=10). At the holding potential of -50 mV, the current amplitude of ACh-sensitive potassium current activated by 100 micronmol/L ACh was (506.6 +/- 186.3) pA (n=9). ACh-sensitive potassium current was sensitive to TEA (tetraethylammonium chloride, 10 mmol/L) and potently inhibited by the small conductance calcium-dependent potassium current (SK) blocker, apamin (1 micromol/L). Iberiotoxin (IBTX), the well-known blocker of big conductance calcium-dependent potassium current (BK), failed to inhibit the amplitude of the ACh-sensitive potassium current at the dose of 200 nmol/L. The dose for half-maximal response (EC50) of the ACh-sensitive potassium current was (33.5 +/- 5.7) micromol/L (n=7). The ACh-sensitive potassium current was sensitive to the GABA (gamma-aminobutyric acid)-A receptor blocker, bicuculline, and strongly inhibited by the selective blocker of the alpha 9-nicotinic ACh receptor, strychnine. Strychnine and bicuculline showed the dose-dependent blocking effect with a half inhibition-maximal response (IC50) of (22.3 +/- 2.6) nmol/L (n=7) and (1.2 +/- 0.4) micromol/L (n=6), respectively.

CONCLUSIONSThis work provides direct evidences that the ACh-sensitive SK current was present on guinea pig cochlear outer hair cells. The activation of the ACh-sensitive SK current was most possibly mediated by a alpha 9-nicotinic ACh receptor.

Animals ; Guinea Pigs ; Hair Cells, Auditory, Outer ; drug effects ; metabolism ; Membrane Potentials ; Patch-Clamp Techniques ; Potassium ; metabolism ; pharmacology ; Potassium Channels ; physiology ; Receptors, Cholinergic ; drug effects ; metabolism

OBJECTIVEThe purpose of this study was to evaluate the maximum binding(Bmax) and affinity(Kd value) changes of acetylcholine receptor (n-AchR) in rat lateral pterygoid muscles after functional mandibule advancement.

METHODS40 five-weeks-old male Sprague-Dawley rats were equally divided into experimental and control group. The mimic functional appliances were used in experiment group and the rats were killed after 1, 3, 7, 14 days. Radio-ligand binding assay (RBA) was applied to determine the maximum binding(Bmax) and Kd value of n-AchR of lateral pterygoid muscle.

RESULTSThe Bmax of n-AchR in experimental group was higher than that in control group and the Kd value always kept in high level.

CONCLUSIONThe functional orthopedics can increase the Bmax of n-AchR in rapid growing rat lateral pterygoid muscles.

Animals ; Binding Sites ; Cell Membrane ; metabolism ; Male ; Mandibular Advancement ; Orthodontic Appliances, Functional ; Pterygoid Muscles ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholinergic ; metabolism

BACKGROUNDSingle-fiber electromyography (SFEMG) abnormality in the extensor digitorum communis (EDC) was reported in ocular myasthenia gravis (OMG), which indicated subclinical involvement beyond extraocular muscles in OMG patients. The relationship between the abnormal findings of SFEMG in EDC and the probability for OMG to develop generalized myasthenia gravis (GMG) is unknown. This retrospective study aimed to determine the predictive value of abnormality of SFEMG in EDC of OMG patients.

METHODSOne-hundred and two OMG patients underwent standard clinical diagnosis process and SFEMG test in EDC muscle when diagnosed and were clinically followed up for 5 years. The SFEMG data were compared between different clinical groups according to thymus status, onset age, and different outcome of OMG developing. Chances of progressing to GMG were compared between two different groups according to SFEMG and repetitive nerve stimulation (RNS) results, acetylcholine receptor antibody (AchRAb) titer, thymus status, and onset age.

RESULTSAbnormal SFEMG results were observed in 84 (82.4%) patients. The mean jitter, percentage of jitter >55 μs (%), and blocking were higher in OMG patients than in healthy volunteers. There were no statistical differences in jitter analysis between thymoma group and non-thymoma group (P = 0.65), or between the later OMG group and the later GMG group (P = 0.31), including mean jitter, percentage of jitter >55 μs (%), and blocking. Elderly group (≥45 years old) had a higher mean jitter than younger group (t = 2.235, P = 0.028). Total 55 OMG developed GMG, including 47 in abnormal SFEMG group while 8 in normal SFEMG group. There was no statistical difference in the conversion rates between the two groups (χ2 = 0.790, P = 0.140). RNS abnormality, AchRab titer, or onset age had no correlation with OMG prognosis (P = 0.150, 0.070, 0.120, respectively) while thymoma did (χ2 = 0.510, P = 0.020).

CONCLUSIONSFEMG test in the EDC showed high abnormality in OMG, suggesting subclinical involvement other than extraocular muscles. Nevertheless, the abnormal jitter analysis did not predict the prognosis of OMG according to clinical follow-up.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Electromyography ; methods ; Humans ; Middle Aged ; Myasthenia Gravis ; metabolism ; pathology ; physiopathology ; Prognosis ; Receptors, Cholinergic ; metabolism ; Retrospective Studies ; Young Adult

Acetylcholine ; metabolism ; physiology ; Animals ; Cholinergic Agonists ; pharmacology ; Male ; Muscle Contraction ; drug effects ; physiology ; Muscle Relaxation ; drug effects ; physiology ; Muscle, Smooth ; drug effects ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Receptors, Cholinergic ; physiology ; Synaptic Transmission ; drug effects ; Urinary Bladder ; drug effects ; innervation ; physiopathology

BACKGROUND/AIMS: Urocortin 1, a corticotropin-releasing factor related peptide, increases colonic motility under stressful conditions. We investigated the effect of urocortin 1 on colonic motility using an experimental model with isolated rat colon in which the blood flow and intestinal nerves were preserved. Furthermore, we assessed whether this effect was mediated by adrenergic or cholinergic nerves. METHODS: Colonic motility was measured in the proximal and distal parts of resected rat colon. The colon resected from the peritoneum was stabilized, and then urocortin 1 (13.8, 138, 277, and 1,388 pM) was administered via a blood vessel. Motility index was measured in the last 5 min of the 15 min administration of urocortin 1 and expressed as percentage change from baseline. Subsequently, the change in motility was measured by perfusing urocortin 1 in colons pretreated with phentolamine, propranolol, hexamethonium, atropine, or tetrodotoxin. RESULTS: At concentrations of 13.8, 138, 277, and 1,388 pM, urocortin 1 increased the motility of proximal colon (20.4+/-7.2%, 48.4+/-20.9%, 67.0+/-25.8%, and 64.2+/-20.9%, respectively) and the motility of distal colon (3.3+/-3.3%, 7.8+/-7.8%, 71.1+/-28.6%, and 87.4+/-32.5%, respectively). The motility induced by urocortin 1 was significantly decreased by atropine to 2.4+/-2.4% in proximal colon and 3.4+/-3.4% in distal colon (p<0.05). However, tetrodotoxin, propranolol, phentolamine, and hexamethonium did not inhibit motility. CONCLUSIONS: Urocortin 1 increased colonic motility and it is considered that this effect was directly mediated by local muscarinic cholinergic receptors.
Animals ; Colon/*drug effects/physiology ; Injections, Intravenous ; Male ; Muscle Contraction/drug effects ; Neurotransmitter Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholinergic/chemistry/metabolism ; Urocortins/isolation & purification/*pharmacology

PURPOSE: Central nervous system (CNS) and cardiovascular system (CVS) side effects of anticholinergic agents used to treat overactive bladder (OAB) are underreported. Hence, this review aimed to focus on the mechanisms of CNS and CVS side effects of anticholinergic drugs used in OAB treatment, which may help urologists in planning the rationale for OAB treatment. MATERIALS AND METHODS: PubMed/MEDLINE was searched for the key words "OAB," "anticholinergics," "muscarinic receptor selectivity," "blood-brain barrier," "CNS," and "CVS side effects." Additional relevant literature was determined by examining the reference lists of articles identified through the search. RESULTS: CNS and CVS side effects, pharmacodynamic and pharmacokinetic properties, the metabolism of these drugs, and the clinical implications for their use in OAB are presented and discussed in this review. CONCLUSIONS: Trospium, 5-hydroxymethyl tolterodine, darifenacin, and solifenacin seem to have favorable pharmacodynamic and pharmacokinetic properties with regard to CNS side effects, whereas the pharmacodynamic features of darifenacin, solifenacin, and oxybutynin appear to have an advantage over the other anticholinergic agents (tolterodine, fesoterodine, propiverine, and trospium) with regard to CVS side effects. To determine the real-life situation, head-to-head studies focusing especially on CNS and CVS side effects of OAB anticholinergic agents are urgently needed.
Benzhydryl Compounds ; Benzilates ; Benzofurans ; Cardiovascular System* ; Central Nervous System* ; Cholinergic Antagonists* ; Cresols ; Mandelic Acids ; Metabolism ; Pyrrolidines ; Quinuclidines ; Receptors, Muscarinic ; Tetrahydroisoquinolines ; Urinary Bladder, Overactive* ; Solifenacin Succinate

OBJECTIVETo investigate the effect of penehyclidine hydrochloride on glutamate (Glu)release and N-methyl-D-aspartate receptor (NMDAR)1 expression in hippocampus CA1 with global cerebral ischemia/reperfusion rats.

METHODSSixty male Wistar rats were randomly allocated into three groups; group A received sham operation; group B received ischemia/reperfusion; group C received penehyclidine hydrochloride treatment (2 mg/kg) before ischemia/reperfusion (n=20). Global cerebral ischemia was induced according to Pulsinelli-Brierley method. All animals were divided into two experiments: (I) Microdialysis plus HPLC/FD were used to detect Glu level after reperfusion 1 h, 3 h, 6 h. (II) After reperfusion 3 h, the animals were decapitated on ice and the brains were immediately removed to detect NMDAR1 expression in CA1 area by immunohistochemistry.

RESULTSAfter penehyclidine hydrochloride treatment, extracellular Glu level in CA1 were significantly decreased compared with those of control group (P < 0.05 or 0.01); Total integrated OD, average gray value and positive-cell area of NMDAR1 in CA1 were also significantly decreased compared with those of control group (P < 0.05 or 0.01).

CONCLUSIONPenehyclidine hydrochloride might has protective effect in hippocampus CA1 on global cerebral ischemia/reperfusion animals. The protective mechanism might be involved in inhibiting Glu release and NMDAR1 expression.

Animals ; Brain Ischemia ; metabolism ; physiopathology ; CA1 Region, Hippocampal ; metabolism ; Cholinergic Antagonists ; pharmacology ; Glutamic Acid ; metabolism ; Male ; Quinuclidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Reperfusion Injury ; metabolism ; prevention & control