K+-induced neurogenic relaxation of rat distal colon

Relaxations of segments of rat distal colon were elicited by hypertonic sol utions of potassium (K+; final concentration, 20.8 or 50.8 mM). The initial part of the response to K+ was antagonized by the nerve blocker tetrodotox in. This effect could, moreover, be significantly antagonized by apamin (a blocker of K+ channels), reactive blue 2 (a P-2y-purinoceptor antagonist), N-G-nitro-L-arginine (an inhibitor of NO synthase), 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxaline-1-one (ODQ; an inhibitor of soluble guanylyl cyclase), or N -[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89; an inhibi tor of cAMP-dependent protein kinase). Sodium nitroprusside (a donor of NO) and vasoactive intestinal peptide (VIP) both relaxed the tissues. The resp onse to sodium nitroprusside was abolished by ODQ and unaffected by H-89, a nd that to VIP was partially inhibited by VIP10-28 (a VIP receptor antagoni st), ODQ, or H-89. When combining reactive blue 2 and N-G-nitro-L-arginine, the response to 50.8 mM K+ was reduced by similar to 70% and was abolished by the concomitant administration of these antagonists and VIP10-28. ATP, NO, and VIP may, thus, be inhibitory neurotransmitters in rat distal colon.