ABSTRACT
OBJECTIVE: To investigate changes in (1) the colonic response to acetylcholine (Ach), (2) the muscarinic (M) receptors in the colon, and (3) the levels of colonic contraction-related proteins after a spinal cord injury (SCI). METHOD: We divided 16 Sprague-Dawley rats into 2 groups: the control group and the SCI group. A spinal cord transection was performed surgically at the T10 vertebral level. After 1 week, the entire colon was divided into 2 segments, the proximal and distal colon. Each segment was mounted in a longitudinal or circular muscle direction in a 10-ml organ bath. We determined the intergroup differences as percentage changes in contractility after Ach treatment alone, Ach treatment with M2 receptor antagonist (AQ-RA741) pretreatment, and Ach treatment with M3 receptor antagonist (4-DAMP) pretreatment. Western blot analyses were performed to determine the expression level of RhoA, and heat shock protein 27 (HSP27). RESULTS: Compared to the control rats, the SCI rats showed an increased response to Ach along both the directions in the proximal colon (p<0.05). Compared to the control group, in the SCI group, the Ach response was significantly different in the proximal segment under AQ-RA741 pretreatment (p<0.05) and in the distal segment under 4-DAMP pretreatment (p<0.05). Findings of the western blot analyses showed a significant decrease in the level of protein gene product 9.5 in the proximal and distal colon and a significant increase in the level of RhoA and HSP27 in the proximal colon of the SCI rats. CONCLUSION: Our results suggest that changes in colonic contractility after SCI are partly attributable to changes in the M receptor subtypes.
Subject(s)
Animals , Rats , Acetylcholine , Baths , Blotting, Western , Colon , HSP27 Heat-Shock Proteins , Muscle, Smooth , Muscles , Piperidines , Proteins , Rats, Sprague-Dawley , Receptors, Muscarinic , Spinal Cord , Spinal Cord InjuriesABSTRACT
The fifth muscarinic receptor (M5), the last one of the muscarinic receptor family to be cloned, has the same basic formation characterization as G-protein coupled receptor family. M5 transduces signals by coupling with G-proteins, which then modulate the activities of a number of effector enzymes and ion channels. As M5 also plays a variety of prominent physiological roles by regulating central transmitters NO and DA, it has been considered as a novel drug therapy target for drug addiction, dysfunction of dopamine-ergic nervous system, Alzheimers disease and cerebral ischemia.
ABSTRACT
Objective To study the relationship between IP 3 and detrusor cell contraction mediated by M 3R. Methods [3H]-IP contents of human cultured detrusor cells were detected after stimulated by carbachol,atropine,methoctramine and 4-DAMP respectively. Results [3H]-IP contents increased with carbachol concentration.On the different concentrations (10 -9、10 -8、10 -7、10 -6、10 -5、10 -4 mmol/L )of 4-DAMP,[3H]-IP contents were 3 926.57?273.29、2 780.52?211.09、2436.84?153.62、1 973.22?164.71、1 372.38?141.35 and 1 107.98?920.45 cpm respectively.On the some concertrations of Atropine,[3H]-IP contents were 3 602.69?280.17,2 891.31?207.45,1 983.97?145.74,1 269.57? 105.31,1 106.37?75.23,927.50?77.36/min,respectively.On the same concentrations of methoctramine, the [3H]-IP contents was 4 462.74?360.69、3 938.61?327.13、3 315.45?270.36、3 063.19? 246.79、2927.37?226.45 and 2 836.55?241.63 cpm.This donoted that 4-DAMP and atropine signficantly inhibited the effect of carbachol on PI decomposition(P0.05). Conclusions M 3R is much related to IP 3.
ABSTRACT
Stimulation of muscarinic receptors by carbachol (CCh) in the circular smooth muscle of the guinea pig gastric antrum causes muscle contraction. In the present study, muscarinic receptor subtype controlling the muscle contraction in response to CCh was studied using putative muscarinic receptor antagonists. Isometric force of the isolated circular muscle strips was measured in an organ bath. CCh contracted the muscle in a dose-dependent way, and each of the three muscarinic receptor antagonists, 4-diphenylacetoxy-N-methylpeperdine methiodide (4-DAMP), methoctramine and pirenzepine shifted the concentration-response curves to the right without significantly reducing the maximum force. The affinities of the muscarinic antagonists (pA2 values) obtained from Schild plot analysis were 10.15, 7.05 and 6.84 for 4-DAMP, methoctramine and pirenzepine, respectively. These results suggest that the M3-subtype mainly mediate the muscle contraction in response to CCh in guinea pig gastric antrum.
Subject(s)
Animals , Baths , Carbachol , Guinea Pigs , Guinea , Muscarinic Antagonists , Muscle Contraction , Muscle, Smooth , Pirenzepine , Pyloric Antrum , Receptors, MuscarinicABSTRACT
The fifth muscarinic receptor (M5), the last one of the mus ca rinic receptor family to be cloned, has the same basic formation characterizatio n as G-protein coupled receptor family. M5 transduces signals by coupling with G-proteins, which then modulate the activities of a number of effector enzymes and ion channels. As M5 also plays a variety of prominent physiological roles by regulating central transmitters NO and DA, it has been considered as a novel dr ug therapy target for drug addiction, dysfunction of dopamine-ergic nervous sys tem, Alzheimers disease and cerebral ischemia.