By using selective tachykinin NK1 and NK2 receptor antagonists and agonists, we studied the excitatory non-adrenergic non-cholinergic transmission to the circular muscle of the corpus of guinea-pig stomach by the sucrose-gap method. After elimination of inhibitory junction potentials by apamin (0.1 microM), L-nitroarginine (30 microM) and tetraethylammonium (10 mM), electrical field stimulation (10 Hz) in the presence of atropine (1 microM) and nifedipine (1 microM) evoked a pure excitatory junction potential and contraction. The selective tachykinin NK2 receptor antagonist, MEN 11420, concentration-dependently inhibited the non-adrenergic non-cholinergic excitatory junction potential (EC50=0.09 microM) and contraction (EC50=0.04 microM) evoked by electrical field stimulation. On the other hand, the selective NK1 receptor antagonist GR 82334 (3 microM) only slightly (by about 30%) inhibited the excitatory junction potential while leaving the contraction unaffected. The combined administration of GR 82334 (1 microM) and MEN 11420 (0.3 microM) produced an additive inhibition of the excitatoryjunction potential, significantly larger than that produced by each antagonist alone. In the presence of both GR 82334 (1 microM) and MEN 11420 (0.3 microM), the P2 purinoreceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (30 microM) remarkably inhibited the fast component of the excitatory junction potential. In the presence of atropine (1 microM), indomethacin (3 microM) and guanethidine (3 microM) either the selective NK2 receptor agonist, [betaAla8]neurokinin A (4-10) (0.01 microM), or the selective NK1 receptor agonist, [Sar9]substance P sulfone (0.3 microM), produced tetrodotoxin-(1 microM) and nifedipine-(1 microM) resistant depolarization and contraction. The [Sar9]substance P sulfone (0.3 microM)-induced contraction, but not that induced by [betaAla8]neurokinin A (4 10) (0.01 microM), was potentiated by apamin (0.1 microM) plus L-nitroarginine (30 microM). In the presence of atropine (1 microM), indomethacin (3 microM), guanethidine (3 microM), apamin (0.1 microM) and L-nitroarginine (30 microM), the selective tachykinin NK2 and NK1 receptor agonists, [betaAla8]neurokinin A (4-10) and [Sar9]substance P sulfone, both produced a concentration-dependent depolarization and contraction of the circular muscle. MEN 11420 inhibited the responses to [[Ala8]neurokinin A (4-10) without affecting the responses to [Sar9]substance P sulfone, while GR 82334 inhibited the responses to [Sar9]substance P sulfone but not that to [betaAla8]neurokinin A (4-10). These data provide evidence that tachykinin NK2 receptors predominantly mediate the non-adrenergic non-cholinergic excitatory transmission to the circular muscle of the corpus of guinea-pig stomach. In addition, after blocking the non-adrenergic non-cholinergic inhibitory junction potential by apamin, L-nitroarginine and tetraethylammonium, the fast component of the non-adrenergic non-cholinergic excitatory junction potential could be mediated by adenosine triphosphate.