Inhibitory responses to exogenous adenosine in murine proximal and distal colon.
The aims of the present study were firstly, to characterize pharmacologically the subtypes of P(1) purinoreceptors involved in the inhibitory effects induced by exogenous adenosine in longitudinal smooth muscle of mouse colon, and secondly, to examine differences in the function and distribution of these receptors between proximal and distal colon. Adenosine (100 microM-3 mM) caused a concentration-dependent reduction of the amplitude of spontaneous contractions in the proximal colon, and muscular relaxation in the distal colon. In the proximal colon, adenosine effects were antagonized by a selective A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nM), but were not modified by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 microM) or by 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino)- [1,2,4]triazolo[1,5-c]quinazoline (MRS 1220, 0.1 microM), selective A(2) and A(3) receptor antagonists, respectively. In the distal colon, adenosine effects were antagonized by DPCPX, DMPX, and by a selective A(2B) receptor antagonist, 8-[4-[((4-cyanophenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl) xanthine (MRS 1754, 10 microM), but not by 8-(3-chlorostyryl)-caffeine (CSC, 10 microM), a selective A(2A) receptor antagonist, or by MRS 1220. Tetrodotoxin (TTX 1 microM), the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM), an inhibitor of soluble guanylyl cyclase, reduced adenosine effects only in distal colon. In addition, L-NAME induced a further reduction of adenosine relaxation in the presence of DPCPX, but not in the presence of MRS 1754. From these results we conclude that, in the murine proximal colon, adenosine induces inhibitory effects via TTX-insensitive activation of A(1) receptor. In the distal colon, adenosine activates both A(1) and A(2B) receptors, the latter located on enteric inhibitory neurons releasing NO.
Zizzo
Maria Grazia
MG
Dipartimento di Biologia Cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Mulè
Flavia
F
Serio
Rosa
R
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C110041:9-chloro-2-(2-furyl)-5-phenylacetylamino(1,2,4)triazolo(1,5-c)quinazoline; D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines; D018047:Receptors, Purinergic P1; D014230:Triazoles; D014970:Xanthines; D009569:Nitric Oxide; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D052250:Nitric Oxide Synthase Type III; D000241:Adenosine; D013805:Theobromine; D019331:NG-Nitroarginine Methyl Ester