The purpose of this study was to assess the role of tachykinins (TK) in mediating nonadrenergic noncholinergic (NANC) contractions produced by electrical field stimulation (EFS) in the longitudinal muscle of the rat ileum. In the presence of atropine (1 μM), guanethidine (5 μM), and L-nitroarginine (L-NNA, 200μM), EFS (0.5ms pulse duration, 120 V, 1-20 Hz for 2 min) produced a frequency-dependent slowly-developing tonic contraction with superimposed phasic contractions (´on´-contraction) followed by off slowly-decreasing tonic and superimposed phasic contractions (´off-contraction) of mucosa-free longitudinal oriented muscle strip. These EFS induced responses were blocked by tetrotoxin. NK_(1) receptor selective antagonist L-732,138 strongly inhibited the EFS-induced excitatory responses. However NK_(2) receptor selective antagonist, GR 159897 and NK_(3) receptor selective antagonist SB 222200 did not significantly inhibited the responses. NK_(1) receptor selective agonist 〔Sar^(9),Met(O_(2)^(11)〕Substance P and NK_(2) receptor selective agonist 〔β-Ala^(8)〕-neurokinin A (4-10) induced tonic contraction with superimposed phasic contractions of longitudinal oriented muscle strip and almost blocked by selective antagonist L-732,138 and GR 159897, respectively. But NK_(3) receptor selective agonist senktide did not showed any effect. Nifedipine (1 μM) abolished the contraction produced either by EFS or by the TK receptor agonists 〔Sar^(9),Met(O_(2)^(11)〕Substance P or 〔β-Ala^(8)〕-neurokinin A (4-10).
It is concluded that, in the longitudinal muscle of rat ileum, both NK_(1) and NK_(2) receptors modulated the responses to exogenous tachykinins, whereas NK_(1) is mainly involved in NANC neuromuscular contraction.
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