ABSTRACT
In order to investigate the role of non-adrenergic non-cholinergic nerves in regulating mechanical and electrical activity of gastric circular smooth muscle, the effects of ATP and its analogues on gastric motility and electrical activities were observed in guinea-pig. In organ bath system, isometric force of the circular smooth muscle of guinea-pig gastric antrum was measured. Electrical activity of the muscle was recorded by using intracellular microelectrode. Electrical and mechanical activities were recorded by chart recorder. ATP and 2-MeSATP potentiated the mechanical activity but did not affect electrical activity in gastric circular smooth muscle. ATP and 2-MeSATP-induced contraction was effectively blocked by nonselective P2y-purinoceptor antagonist, reactive-blue-2 and suramin, but ATP-induced contraction was not blocked by alpha,beta-MeATP-induced desensitization of P2x-purinoceptors. However, alpha,beta-MeATP, P2x-purinoceptor agonist, attenuated slow waves with membrane hyperpolarization and inhibited contraction. The relaxation by beta,gamma-MeATP was blocked by alpha,beta-MeATP-induced desensitization of P2x-purinoceptors. ATP-induced contraction was blocked by external calcium-free, but not by nicardipine, a L-type calcium channel blocker. Indomethacin, a nonselective cyclooxygenase inhibitor, did not block ATP-induced contraction. The results suggest that: (1) ATP- and analogues-induced contraction is mediated by P2y-purinoceptor, whereas alpha,beta-MeATP-induced relaxation by P2x-purinoceptor in guinea-pig gastric antral circular smooth muscle. (2) ATP-induced contraction is dependent on extracellular calcium, but Ca2+ entry is not mediated by L-type calcium channel. (3) Prostaglandins are not involved in ATP- and analogue-induced contraction of gastric circular smooth muscle in guinea-pigs, and alpha,beta-MeATP-induced relaxation is related to membrane hyperpolarization.
Subject(s)
Adenosine Triphosphate/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Purinergic Agonists , Adenosine Triphosphate/analogs & derivatives , Animals , Electrophysiology , Guinea Pigs , In Vitro Techniques , Microelectrodes , Muscle Contraction/physiology , Muscle, Smooth/physiology , Pyloric Antrum/drug effects , Pyloric Antrum/physiology , Thionucleotides/pharmacologyABSTRACT
AIM: To investigate the relationship between hyposmotic membrane stretch and muscarinic receptor agonist-induced depolarization of membrane potential in antral gastric circular myocytes of guinea-pig. METHODS: Using whole cell patch-clamp technique recorded membrane potential and current in single gastric myocytes isolated by collagenase. RESULTS: Hyposmotic membrane stretch hyperpolarized membrane potential from -60.0mV+/-1.0mV to -67.9mV+/-1.0mV. TEA (10 mmol/L), a nonselective potassium channel blocker significantly inhibited hyposmotic membrane stretch-induced hyperpolarization. After KCl in the pipette and NaCl in the external solution were replaced by CsCl to block the potassium current, hyposmotic membrane stretch depolarized the membrane potential from -60.0 mV+/-1.0mV to -44.8 mV+/-2.3mV (P<0.05), and atropine (1 micromol/L) inhibited the depolarization of the membrane potential. Muscarinic receptor agonist Carbachol depolarized membrane potential from -60.0mV+/-1.0mV to -50.3 mV+/-0.3mV (P<0.05) and hyposmotic membrane stretch potentiated the depolarization. Carbachol induced muscarinic current (I( cch )) was greatly increased by hyposmotic membrane stretch. CONCLUSION: Hyposmotic membrane stretch potentiated muscarinic receptor agonist-induced depolarization of membrane potential, which is related to hyposmotic membrane stretch-induced increase of muscarinic current.
