The NANC relaxation of the human ileal longitudinal and circular muscles is inhibited by MRS 2179, a P2 purinoceptor antagonist.
OBJECTIVE
Functional innervation of the human small intestine may be different from that of experimental animals. These experiments set out to assess the mediating roles of P(2) purinoceptors in the non-adrenergic, non-cholinergic (NANC) relaxation of the human ileum longitudinal and circular muscles.


METHODS
In organ bath experiments NANC relaxations were evoked by electrical field stimulation (EFS). The relaxant effects of ATP and sodium nitroprusside were also examined.


RESULTS
In the longitudinal muscle, relaxation in response to EFS (2 or 10 Hz for 30 s) or the relaxant effect of exogenous ATP were strongly inhibited or abolished, respectively, by the P(2) purinoceptor antagonist MRS 2179 (10 microM). MRS 2179 had a smaller effect at 3 microM. The NANC relaxation was also inhibited by apamin (3 microM), but not by N(G)-nitro-L-arginine (100 microM), an inhibitor of nitric oxide synthesis. Both apamin (3 microM) and MRS 2179 (3 microM, a concentration below the effective range if administered alone) strongly inhibited the NANC response in preparations pretreated with the nitric oxide synthase inhibitor. NANC relaxations of the circular muscle were also inhibited by MRS 2179 (3-10 microM).


CONCLUSIONS
MRS 2179-sensitive P(2) purinoceptors play a mediating role the NANC relaxation in the ileal longitudinal and circular muscle. There seems to be a supra-additive relationship between the purinergic and nitrergic mechanisms in the longitudinal muscle.
Undi
Sarolta
S
Department of Pharmacology and Pharmacotherapy, University Medical School of Pecs, Pecs, Hungary.
Benko
Rita
R
Wolf
Matyas
M
Illenyi
Laszlo
L
Vereczkei
Andras
A
Kelemen
Dezsö
D
Cseke
Laszlo
L
Csontos
Zsolt
Z
Horvath
Ors Peter
OP
Bartho
Lorand
L
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists
D004791:Enzyme Inhibitors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D020030:Nitric Oxide Donors; D058919:Purinergic P2 Receptor Antagonists; D009599:Nitroprusside; D019335:Nitroarginine; D001030:Apamin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate