Evidence for an apamin‐sensitive, but not purinergic, component in the nonadrenergic noncholinergic relaxation of the rat gastric fundus

The involvement of adenosine triphosphate (ATP) and carbon monoxide (CO) in the non‐nitrergic nonpeptidergic component of high‐frequency electrical field stimulation (EFS)‐induced nonadrenergic noncholinergic (NANC) relaxation of longitudinal muscle strips from the rat gastric fundus was investigated. Under NANC conditions (1 μ M atropine+5 μ M guanethidine), N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 1 m M ) slightly reduced the amplitude, but did not affect the area under the curve (AUC) of EFS (13 Hz, 2 min)‐induced relaxation of 9,11‐dideoxy‐9 α ,11 α ‐methanoepoxy prostaglandin F 2 α (U46619, 0.1 μ M )‐precontracted strips. With L ‐NAME (1 m M ) plus α ‐chymotrypsin (1 U ml −1 ), the amplitude and the AUC of relaxation were reduced to approximately two‐third and one‐third of controls, respectively. Pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (100 μ M ), apamin (0.3 μ M ), desensitization to ATP, suramin (100 μ M ), zinc protoporphirin IX (300 μ M ) or ferrous haemoglobin (100 μ M ) did not inhibit the component of relaxation resistant to L ‐NAME plus α ‐chymotrypsin.L ‐NAME (1 m M ) plus anti‐vasoactive intestinal peptide (VIP) serum (1 : 100) reduced the amplitude and the AUC of relaxation to a similar extent as L ‐NAME (1 m M ) plus α ‐chymotrypsin (1 U ml −1 ). Adding apamin (0.1 μ M ) to L ‐NAME (1 m M ) plus anti‐VIP serum (1 : 100) further reduced the amplitude and the AUC of relaxation. These findings suggest that the non‐nitrergic nonpeptidergic component of NANC relaxation of the rat gastric fundus induced by high‐frequency stimulation is mediated by a neurotransmitter thatacts through apamin‐sensitive mechanisms, that is neither ATP nor CO.British Journal of Pharmacology (2004) 143 , 785–793. doi: 10.1038/sj.bjp.0705993