A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels.
OBJECTIVE
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.


METHODS
Mechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension.


RESULTS
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, BK(Ca) channel blockers, significantly reduced adenosine effects, whilst 4-aminopyridine, a K(v) blocker, apamin, a small conductance Ca2+-activated K+ (SK(Ca)) channel blocker, charybdotoxin, an intermediate conductance Ca2+-activated K+ (IK(Ca)) and BK(Ca) 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.


CONCLUSIONS
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 BK(Ca) and SK(Ca) potassium channels. This study would provide new insight in the pharmacology of purinergic receptors involved in the modulation of the gastrointestinal contractility.
Zizzo
Maria Grazia
MG
Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Viale delle Scienze, Palermo I-90128, Italy.
Bonomo
Alessandra
A
Belluardo
Natale
N
Mulè
Flavia
F
Serio
Rosa
R