ATP AND NITRIC-OXIDE - INHIBITORY NANC NEUROTRANSMITTERS IN THE LONGITUDINAL MUSCLE-MYENTERIC PLEXUS PREPARATION OF THE RAT ILEUM

1 The nature of neurotransmitter(s) involved in non-adrenergic non-cho linergic (NANC) relaxations induced by electrical stimulation (10 s tr ains, 1-8 Hz) was investigated in the precontracted longitudinal muscl e-myenteric plexus preparation of the rat ileum. 2 Electrical stimulat ion of the tissue induced complex responses, consisting of a primary c ontraction, a primary relaxation, an off-relaxation and a rebound cont raction, which were all tetrodotoxin(TTX)-sensitive. 3 Vasoactive inte stinal polypeptide (VIP) and carbon monoxide (GO) did not induce relax ations. alpha-Chymotrypsin did not reduce the relaxations induced by e lectrical stimulation, while zinc protoporphyrin IX had non-specific e ffects.4 Nitric oxide (NO) induced concentration-dependent relaxations . N-G-nitro-L-arginine methylester (L-NAME) abolished the primary cont ractions and off-relaxations, while it partially reduced the primary r elaxations. 5 ATP induced relaxations and ATP-desensitization of the t issues partially reduced the primary relaxations. Suramin and reactive blue 2 did not consistently influence the primary relaxations. 6 The ATP-induced relaxations were not influenced by L-NAME or TTX. The inhi bitory effect of ATP-desensitization and L-NAME did not summate. 7 The cyclic AMP content of the tissue did not increase upon electrical sti mulation or after addition of NO or ATP. The cyclic GMP content of the tissue increased upon electrical stimulation and addition of NO, but not after addition of ATP. 8 It is concluded that the relaxation induc ed by electrical stimulation consists of two types of responses. The o ff-relaxation is completely nitrergic, while the primary relaxation is mediated by NO, ATP and an as yet unknown transmitter which is not VI P or CO.