A1 ADENOSINE RECEPTOR MODULATION OF CONTRACTILITY IN MOUSE DUODENUM LONGITUDINAL MUSCLE.

Experimental evidence suggests that adenosine is involved in the regulation of gastrointestinal functions. In the present study we examined the influence of adenosine on the contractile activity of mouse duodenum longitudinal muscle. Reverse transcription-polymerase chain reaction revealed the expression of all the adenosine receptors in whole thickness duodenum, being the A2B receptors expressed only in the neuromuscular layer. Mechanical activity of longitudinally oriented duodenal segments was recorded in vitro as changes in isometric tension. Adenosine produced concentration-dependent relaxation, markedly reduced by DPCPX, A1 receptor antagonist, but unaffected by DMPX or MRS 1220, A2 and A3 receptor antagonists respectively. In the presence of tetrodotoxin, neuronal blocker, or of L-NAME, nitric oxide synthase blocker, the effects of adenosine were still evident. Indeed, adenosine-induced relaxation was significantly antagonized by cyclopiazonic acid, a specific inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase, or by TEA, big conductance Ca2+-dependent K+ channels (BKCa ) blocker. Adenosine, at a concentration which hardly affects the spontaneous contractions, inhibited neurally evoked cholinergic contraction. This effect was reversed only by A1 receptor antagonist. In conclusion, adenosine exerts an inhibitory control on mouse duodenal contractility via muscular A1 receptors, through a mechanism involving SR Ca2+-ATPase and increase of potassium conductances. Moreover, A1 receptors located at prejunctional level negatively affect Ach neural release.