Effect Of P2X Purinocepter On Spontaneous Contraction Of Gastric Antral Circular Muscle In Guinea Pig

Non-adrenergic non-cholinergic nerves distribute in gastrointestinal tracts extensively and play an important role in modulation of their functions. In 1970, Burnstock and his colleagures firstly advanced that ATP is one of the NANC neurotranmitters. Since then, many studies supported this hypothesis. In vivo, ATP takes effect mainly through G-protein-coupled P2Y purinoceptors and ligand-gated P2X purinoceptors. Effects of P2X purinoceptors are different in different animals and different parts, and the mechanisms are unclear. In our present study, we investigated the effect of P2X purinoceptor agonistα,β-MeATP on the smooth muscle spontaneous contractions in antral circular muscle of guinea pig and explored the preliminary mechanisms by using patch clamp and calcium imaging techniques at the cell level.The results were as follows:â‘ At the tissue level, P2X purinoceptor agonistα,β-MeATP significantly inhibited the spontaneous contractions of antral circular muscle in a dose-dependent manner in guinea pig.â‘¡After pre-incubated with tetrodotoxin(TTX), a neural inhibitor, the inhibitory effect induced byα,β-MeATP was not affected.â‘¢Even in the presence of TEA, a non-selective potassium channel blocker, the spontaneous contractions were still suppressed byα,β-MeATP.â‘£High K+-induced tonic contraction did not inhibited byα,β-MeATP.⑤At the cell level, under the conventional whole-cell configuration, 500μmol/Lα,β-MeATP couldn't affect the membrane potential in the condition of current clamp.â‘¥Under the whole cell configuration,calcium-activated potassium currents and delayed rectifying potassium currents were recorded respectively, andα,β-MeATP affected neither of them.⑦α,β-MeATP also had no effect on L-type calcium currents.⑧α,β-MeATP had no effect on the [Ca²⁺]_i.Our results suggest that P2X purinoceptor agonist induced relaxation of gastric antral smooth muscle of guinea pig, and the effect is not via enteric nerves. The mechanisms of hyperpolarizing membrane potential and inhibiting L-type calcium channel are not involved in the relaxation. The P2X purinoceptor agonist-induced relaxation may be related to reducing the affinity between calmodulin and calcium.