Abstract
This study examines nitric oxide (NO) mediated effects on longitudinal muscle with adherent myenteric ganglia from rat ileum in vitro using NO donors and electrical field stimulation. Electrical field stimulation (20 Hz) caused a biphasic response—a relaxation followed by a contraction. NG-nitro-l-arginine methyl ester almost totally abolished the relaxation and l-arginine restored it. The contraction was unaffected. The NO donors sodium-nitroso-N-acetylpenicillamine (SNAP) and sodium-nitroprusside also induced a biphasic response, a contraction followed by relaxation. Relaxations mediated by neuronally released NO were not blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one suggesting that they are independent of a rise in intracellular cyclic guanylate cyclase. Their amplitude was unaffected by forskolin. The relaxations evoked by NO (or a NO-related substance) liberated from SNAP were blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one indicating a cyclic guanylate cyclase-dependent mechanism of action. Pituitary adenylate cyclase-activating peptide and forskolin, but not vasoactive intestinal peptide or neuropeptide Y, caused a marked left-ward shift of the concentration-response curve of the SNAP-induced relaxation. The contractions induced by SNAP were blocked by methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one and thus, cyclic guanylate cyclase dependent. The SNAP-induced contractions were abolished by pituitary adenylate cyclase-activating peptide and forskolin, but unaffected by vasoactive intestinal peptide or NPY. In conclusion, motor responses evoked by NO released from NO donorsvs. neuronally released NO reveals different mechanisms of action.
Footnotes
-
Send reprint requests to: Dr. Eva Ekblad, Department Physiology and Neuroscience, Section Neuroendocrine CellBiology, Experimental Research Center, E-blocket vån.5, University Hospital, S-221 85 Lund, Sweden.
-
↵1 This work was supported by grants from the Swedish Medical Research Council (Projects 4499 and 00712), Påhlsson’s, Bergwall’s, Viberg’s Foundation and Crafoord Foundations.
- Abbreviations:
- ATP
- adenosine triphosphate
- cAMP
- cyclic adenylate cyclase
- cGMP
- cyclic guanylate cyclase
- DMSO
- dimethyl sulfoxide
- EFS
- electrical field stimulation
- L-NAME
- NG-nitro-l-arginine methyl ester
- MB
- methylene blue
- NADPH
- nicotinamide adenine dinucleotide phosphate
- NO
- nitric oxide
- NOS
- nitric oxide synthase
- NPY
- neuropeptide Y
- ODQ
- 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one
- PACAP
- pituitary adenylate cyclase-activating peptide
- PGF2α
- prostaglandin F2α
- SNAP
- sodium-nitroso-N-acetylpenicillamine
- SNP
- sodium-nitroprusside
- TTX
- tetrodotoxin
- VIP
- vasoactive intestinal peptide
- Received January 24, 1997.
- Accepted June 19, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
