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 P2y-purinoceptor antagonist),NG-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 VIP10–28 (a VIP receptor antagonist), ODQ, or H-89. When combining reactive blue 2 andNG-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 VIP10–28. ATP, NO, and VIP may, thus, be inhibitory neurotransmitters in rat distal colon.
Footnotes
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Send reprint requests to: Dr. Dick S. Delbro, Department of Surgery, Institute of Surgical Sciences, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail:dick.delbro{at}medfak.gu.se
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↵1 This work was supported by The Göteborg Medical Society and the Swedish Medical Research Council (Grants 11611 and 03117).
- Abbreviations:
- TTX
- tetrodotoxin
- NOS
- nitric oxide synthase
- VIP
- vasoactive intestinal peptide
- L-NNA
- NG-nitro-l-arginine
- D-NNA
- NG-nitro-d-arginine
- ODQ
- 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one
- H-89
- N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide
- SNP
- sodium nitroprusside
- Received May 3, 1999.
- Accepted July 22, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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