Aims We investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K+ channels was a downstream event leading to the observed effects. Main methods Mechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension. Key findings Adenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A1 receptor antagonist, but not by A2 and A3 receptor antagonists and mimicked only by the A1 receptor agonist. Adenosine uptake inhibitors did not change adenosine potency. A1 receptor expression was detected at the smooth muscle level. Adenosine responses were insensitive to tetrodotoxin, atropine or nitric oxide synthase inhibitor. Tetraethylammonium and iberiotoxin, BKCa channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a Kv blocker, apamin, a small conductance Ca2+-activated K+ (SKCa) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IKCa) and BKCa channel blocker, or glibenclamide, an ATP-sensitive K+ channel blocker, had no effects. The combination of apamin plus iberiotoxin caused a reduction of the purinergic effects greater than iberiotoxin alone. Significance Adenosine acts as an inhibitory modulator of the contractility of mouse ileal longitudinal muscle through postjunctional A1 receptors, which in turn would induce opening of BKCa and SKCa potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility.
Zizzo, M., Bonomo, A., Belluardo, N., Mule', F., & Serio, R. (2009). A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels. LIFE SCIENCES, 84(21-22), 772-778 [10.1016/j.lfs.2009.03.006].
|Data di pubblicazione:||2009|
|Titolo:||A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels|
|Citazione:||Zizzo, M., Bonomo, A., Belluardo, N., Mule', F., & Serio, R. (2009). A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels. LIFE SCIENCES, 84(21-22), 772-778 [10.1016/j.lfs.2009.03.006].|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.lfs.2009.03.006|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Appare nelle tipologie:||1.01 Articolo in rivista|