Abstract
1. Electrical field stimulation causes neurally-mediated relaxation of the ileocolonic sphincter that is due to activation of non-adrenergic and non-cholinergic (NANC) nerves. Recent studies have suggested that nitric oxide (NO) is the neurotransmitter that mediates relaxation. 2. Using intracellular recording techniques, we have tested whether NANC inhibitory junction potentials (i.j.ps) in the canine ileocolonic sphincter are also mediated by NO. 3. Electrical field stimulation elicited excitatory and inhibitory junction potentials: e.j.ps were blocked by atropine (10(-6) M) and tetrodotoxin (TTX; 10(-6) M); i.j.ps were also blocked by TTX and partially blocked by apamin (10(-6) M). I.j.ps were unaffected by atropine, phentolamine and propranolol (all at 10(-6) M). 4. The arginine analogues, L-NG-nitroarginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), decreased the amplitude of i.j.ps and L-arginine, but not D-arginine, partially restored the i.j.ps. 5. I.j.ps were also inhibited by oxyhaemoglobin (1%), but not by methaemoglobin. 6. Exogenous NO (10(-7) M to 3 x 10(-5) M) caused concentration-dependent hyperpolarizations that were similar in amplitude to the NANC nerve-evoked i.j.ps. Hyperpolarizations to NO were unaffected by L-NAME, but were blocked by oxyhaemoglobin. 7. Tetrodotoxin, L-NAME and oxyhaemoglobin all caused depolarization of resting membrane potential. 8. The specific guanosine 3':5'-cyclic monophosphate phosphodiesterase inhibitor, M&B 22948, caused hyperpolarization, increased the maximum level of hyperpolarization reached during i.j.ps, and increased the duration of i.j.ps. 9. These data further support the hypothesis that NANC neurotransmission in the ileocolonic sphincter is mediated by NO or an NO-releasing compound.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Banks B. E., Brown C., Burgess G. M., Burnstock G., Claret M., Cocks T. M., Jenkinson D. H. Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Nature. 1979 Nov 22;282(5737):415–417. doi: 10.1038/282415a0. [DOI] [PubMed] [Google Scholar]
- Boeckxstaens G. E., Pelckmans P. A., Bult H., De Man J. G., Herman A. G., Van Maercke Y. M. Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction. Eur J Pharmacol. 1990 Nov 6;190(1-2):239–246. doi: 10.1016/0014-2999(90)94132-h. [DOI] [PubMed] [Google Scholar]
- Boeckxstaens G. E., Pelckmans P. A., Rampart M., Ruytjens I. F., Verbeuren T. J., Herman A. G., Van Maercke Y. M. GABAA receptor-mediated stimulation of non-adrenergic non-cholinergic neurones in the dog ileocolonic junction. Br J Pharmacol. 1990 Oct;101(2):460–464. doi: 10.1111/j.1476-5381.1990.tb12730.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boeckxstaens G. E., Pelckmans P. A., Rampart M., Verbeuren T. J., Herman A. G., Van Maercke Y. M. Evidence against ATP being the inhibitory transmitter released by nonadrenergic noncholinergic nerves in the canine ileocolonic junction. J Pharmacol Exp Ther. 1990 Aug;254(2):659–663. [PubMed] [Google Scholar]
- Boeckxstaens G. E., Pelckmans P. A., Ruytjens I. F., Bult H., De Man J. G., Herman A. G., Van Maercke Y. M. Bioassay of nitric oxide released upon stimulation of non-adrenergic non-cholinergic nerves in the canine ileocolonic junction. Br J Pharmacol. 1991 May;103(1):1085–1091. doi: 10.1111/j.1476-5381.1991.tb12304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bowman A., Gillespie J. S. Block of some non-adrenergic inhibitory responses of smooth muscle by a substance from haemolysed erythrocytes. J Physiol. 1982 Jul;328:11–25. doi: 10.1113/jphysiol.1982.sp014250. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bult H., Boeckxstaens G. E., Pelckmans P. A., Jordaens F. H., Van Maercke Y. M., Herman A. G. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990 May 24;345(6273):346–347. doi: 10.1038/345346a0. [DOI] [PubMed] [Google Scholar]
- Capiod T., Ogden D. C. The properties of calcium-activated potassium ion channels in guinea-pig isolated hepatocytes. J Physiol. 1989 Feb;409:285–295. doi: 10.1113/jphysiol.1989.sp017497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conklin J. L., Christensen J. Local specialization at ileocecal junction of the cat and opossum. Am J Physiol. 1975 Apr;228(4):1075–1081. doi: 10.1152/ajplegacy.1975.228.4.1075. [DOI] [PubMed] [Google Scholar]
- Costa M., Furness J. B., Humphreys C. M. Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract. Naunyn Schmiedebergs Arch Pharmacol. 1986 Jan;332(1):79–88. doi: 10.1007/BF00633202. [DOI] [PubMed] [Google Scholar]
- Craven P. A., DeRubertis F. R. Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. J Biol Chem. 1978 Dec 10;253(23):8433–8443. [PubMed] [Google Scholar]
- Dalziel H. H., Thornbury K. D., Ward S. M., Sanders K. M. Involvement of nitric oxide synthetic pathway in inhibitory junction potentials in canine proximal colon. Am J Physiol. 1991 May;260(5 Pt 1):G789–G792. doi: 10.1152/ajpgi.1991.260.5.G789. [DOI] [PubMed] [Google Scholar]
- Gillespie J. S., Liu X. R., Martin W. The effects of L-arginine and NG-monomethyl L-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation. Br J Pharmacol. 1989 Dec;98(4):1080–1082. doi: 10.1111/j.1476-5381.1989.tb12650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ignarro L. J., Byrns R. E., Buga G. M., Wood K. S. Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res. 1987 Dec;61(6):866–879. doi: 10.1161/01.res.61.6.866. [DOI] [PubMed] [Google Scholar]
- Ignarro L. J., Kadowitz P. J. The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol. 1985;25:171–191. doi: 10.1146/annurev.pa.25.040185.001131. [DOI] [PubMed] [Google Scholar]
- Kelley M. L., Jr, DeWeese J. A. Effects of eating and intraluminal filling on ileocolonic junctional zone pressures. Am J Physiol. 1969 Jun;216(6):1491–1495. doi: 10.1152/ajplegacy.1969.216.6.1491. [DOI] [PubMed] [Google Scholar]
- Kelley M. L., Jr, Gordon E. A., Deweese J. A. Pressure responses of canine ileocolonic junctional zone to intestinal distention. Am J Physiol. 1966 Sep;211(3):614–618. doi: 10.1152/ajplegacy.1966.211.3.614. [DOI] [PubMed] [Google Scholar]
- Kubota M. Electrical and mechanical properties and neuro-effector transmission in the smooth muscle layer of the guinea-pig ileocecal junction. Pflugers Arch. 1982 Oct 1;394(4):355–361. doi: 10.1007/BF00583701. [DOI] [PubMed] [Google Scholar]
- Kukovetz W. R., Holzmann S., Pöch G. Function of cyclic GMP in acetylcholine-induced contraction of coronary smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1982 Apr;319(1):29–33. doi: 10.1007/BF00491474. [DOI] [PubMed] [Google Scholar]
- Langton P. D., Burke E. P., Sanders K. M. Participation of Ca currents in colonic electrical activity. Am J Physiol. 1989 Sep;257(3 Pt 1):C451–C460. doi: 10.1152/ajpcell.1989.257.3.C451. [DOI] [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- Pahlin P. E., Kewenter J. Reflexogenic contraction of the ileo-cecal sphincter in the cat following small or large intestinal distension. Acta Physiol Scand. 1975 Sep;95(1):126–132. doi: 10.1111/j.1748-1716.1975.tb10034.x. [DOI] [PubMed] [Google Scholar]
- Pahlin P. Extrinsic nervous control of the ileo-cecal sphincter in the cat. Acta Physiol Scand Suppl. 1975;426:1–32. [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Papasova M., Mizhorkova Z. Responses for smooth-muscle strips from the ileo-caecal region to transmural electrical stimulation. Acta Physiol Pharmacol Bulg. 1980;6(3):3–10. [PubMed] [Google Scholar]
- Pelckmans P. A., Boeckxstaens G. E., Van Maercke Y. M., Herman A. G., Verbeuren T. J. Acetylcholine is an indirect inhibitory transmitter in the canine ileocolonic junction. Eur J Pharmacol. 1989 Nov 7;170(3):235–242. doi: 10.1016/0014-2999(89)90544-x. [DOI] [PubMed] [Google Scholar]
- Rapoport R. M., Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res. 1983 Mar;52(3):352–357. doi: 10.1161/01.res.52.3.352. [DOI] [PubMed] [Google Scholar]
- Shuba M. F., Vladimirova I. A. Effect of apamin on the electrical responses of smooth muscle to adenosine 5'-triphosphate and to non-adrenergic, non-cholinergic nerve stimulation. Neuroscience. 1980;5(5):853–859. doi: 10.1016/0306-4522(80)90154-2. [DOI] [PubMed] [Google Scholar]
- Smith T. K., Reed J. B., Sanders K. M. Electrical pacemakers of canine proximal colon are functionally innervated by inhibitory motor neurons. Am J Physiol. 1989 Mar;256(3 Pt 1):C466–C477. doi: 10.1152/ajpcell.1989.256.3.C466. [DOI] [PubMed] [Google Scholar]
- Thornbury K. D., Ward S. M., Dalziel H. H., Carl A., Westfall D. P., Sanders K. M. Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon. Am J Physiol. 1991 Sep;261(3 Pt 1):G553–G557. doi: 10.1152/ajpgi.1991.261.3.G553. [DOI] [PubMed] [Google Scholar]
- Toda N., Baba H., Okamura T. Role of nitric oxide in non-adrenergic, non-cholinergic nerve-mediated relaxation in dog duodenal longitudinal muscle strips. Jpn J Pharmacol. 1990 Jun;53(2):281–284. doi: 10.1254/jjp.53.281. [DOI] [PubMed] [Google Scholar]
- Tomita T. Conductance change during the inhibitory potential in the guinea-pig taenia coli. J Physiol. 1972 Sep;225(3):693–703. doi: 10.1113/jphysiol.1972.sp009964. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tøttrup A., Svane D., Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol. 1991 Mar;260(3 Pt 1):G385–G389. doi: 10.1152/ajpgi.1991.260.3.G385. [DOI] [PubMed] [Google Scholar]
