Vol. 291, Issue 2, 717-724, November 1999

K⁺-Induced Neurogenic Relaxation of Rat Distal Colon¹

Lars Börjesson, Svante Nordgren and Dick S. Delbro

Institute of Surgical Sciences, Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden

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), or N-[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 and N^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.