Tachykinins mediate non-adrenergic,non-cholinergic excitatory neurotransmission to the hamster ileum via NK1 and NK2 receptors

The present study was designed to investigate Substance P (SP) and a related tachykinin, Neurokinin A (NKA), contributions to the excitatory neurotransmission to the circular smooth muscle of the hamster ileum. In the presence of atropine (0.5 microM), guanethidine (3 microM) and NG-nitro-L-arginine methyl ester (L-NAME) (200 microM), electrical field stimulation (EFS) evoked a non-adrenergic, non-cholinergic (NANC) excitatory junction potential (EJP) and contraction of circular smooth muscle. Applications of SP and NKA produced depolarizing and contractile responses in a concentration-dependent fashion. The EJP and contraction were almost abolished by the non-specific tachykininergic antagonist, spantide (3 microM). Application of SP antagonist, L-732,138, (1 microM) markedly inhibited EJP (82.5%) and contraction (68.9%) and completely blocked excitatory responses produced by exogenous application of SP. While application of NKA antagonist, SR48968 (1 microM) completely blocked the depolarising and contractile responses to NKA, it only slightly inhibited those to EFS (17.2% and 31.4% respectively).These results provide evidence that, in the circular muscle of hamster ileum, endogenous tachykinins are the main NANC excitatory neurotransmitters and their action is mediated by both NK1 and NK2 receptors.