Abstract

Relaxations of segments of rat distal colon were elicited by hypertonic solutions 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 tetrodotoxin. 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), orN-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89; an inhibitor of cAMP-dependent protein kinase). Sodium nitroprusside (a donor of NO) and vasoactive intestinal peptide (VIP) both relaxed the tissues. The response to sodium nitroprusside was abolished by ODQ and unaffected by H-89, and that to VIP was partially inhibited by VIP_10–28 (a VIP receptor antagonist), ODQ, or H-89. When combining reactive blue 2 andN^G-nitro-l-arginine, the response to 50.8 mM K⁺ was reduced by ∼70% and was abolished by the concomitant administration of these antagonists and VIP_10–28. ATP, NO, and VIP may, thus, be inhibitory neurotransmitters in rat distal colon.