Comparison of the Pharmacological Profile of S-nitrosothiols, Nitric Oxide and the Nitrergic Neurotransmitter in the Canine Ileocolonic Junction

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1995 Mar 1

PMID 7620707

Citations 8

Authors

J G DE Man

G E Boeckxstaens

B Y DE Winter

T G Moreels

M E Misset

A G Herman

P A Pelckmans

Affiliations

Soon will be listed here.

Abstract

1. In organ bath experiments, hydroquinone (30-100 microM) and hydroxocobalamin (30-100 microM) concentration-dependently inhibited the relaxations induced by NO (0.3-30 microM) but not those by nitroglycerin (GTN, 1 microM) in the canine ileocolonic junction (ICJ). Hydroxocobalamin reduced the relaxation to low frequency (2 Hz) stimulation of the non-adrenergic, non-cholinergic (NANC) nerves, whereas hydroquinone only reduced the NANC nerve-mediated relaxations to electrical stimulation at 16 Hz, 0.5 ms. 2. Relaxations to S-nitroso-L-cysteine (CysNO, 1-30 microM), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-30 microM) were not inhibited by hydroquinone (30-100 microM), hydroxocobalamin (30-100 microM), pyrogallol (30-100 microM) or L-cysteine (1-3 microM). Hydroquinone (100 microM) only reduced the relaxation to 10 microM CysNO. Hydroxocobalamin, but not hydroquinone, pyrogallol or L-cysteine, potentiated the relaxations to the lowest concentration (1 microM) of S-nitrosoglutathione (GSNO, 1-30 microM). 3. In the superfusion bioassay, hydroquinone (100 microM) and hydroxocobalamin (1 microM) concentration-dependently inhibited the biological activity of authentic NO (1-4 pmol) to the same extent as that of the transferable nitrergic factor, released from the canine ICJ in response to NANC nerve stimulation (8-16 Hz, 2 ms). Responses to GTN (10 pmol) or adenosine 5'-triphosphate (10 nmol) were not affected. 4. In conclusion, the nitrosothiols CysNO, SNAP and GSNO relax the canine ileocolonic junction, but these relaxations, pharmacologically, behave differently from the NANC nerve-mediated relaxations. From the bioassay experiments, we conclude that the nitrergic factor, released in response to NANCnerve stimulation of the canine ICJ, behaves pharmacologically like NO but not like a nitrosothiol.Therefore, we suggest NO, and not CysNO, SNAP or GSNO as the inhibitory NANC neurotransmitter in the canine ICJ.

Citing Articles

Influence of antioxidant depletion on nitrergic relaxation in the pig gastric fundus.

Colpaert E, Timmermans J, Lefebvre R Br J Pharmacol. 2002; 135(4):917-26.

PMID: 11861319 PMC: 1573215. DOI: 10.1038/sj.bjp.0704553.

Influence of bilirubin and other antioxidants on nitrergic relaxation in the pig gastric fundus.

Colpaert E, Lefebvre R Br J Pharmacol. 2000; 129(6):1201-11.

PMID: 10725269 PMC: 1571952. DOI: 10.1038/sj.bjp.0703176.

Effects of superoxide anion generators and thiol modulators on nitrergic transmission and relaxation to exogenous nitric oxide in the sheep urethra.

Garcia-Pascual A, Labadia A, Costa G, Triguero D Br J Pharmacol. 2000; 129(1):53-62.

PMID: 10694202 PMC: 1621122. DOI: 10.1038/sj.bjp.0703000.

Effects of hydroxocobalamin and carboxy-PTIO on nitrergic transmission in porcine anococcygeus and retractor penis muscles.

Li C, Rand M Br J Pharmacol. 1999; 127(1):172-6.

PMID: 10369470 PMC: 1565983. DOI: 10.1038/sj.bjp.0702496.

Effect of thiol modulators and Cu/Zn superoxide dismutase inhibition on nitrergic relaxations in the rat gastric fundus.

DE Man J, DE Winter B, Boeckxstaens G, Herman A, Pelckmans P Br J Pharmacol. 1996; 119(5):1022-8.

PMID: 8922754 PMC: 1915936. DOI: 10.1111/j.1476-5381.1996.tb15773.x.

References

Ignarro L, Lippton H, Edwards J, Baricos W, HYMAN A, Kadowitz P . Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther. 1981; 218(3):739-49. View

Kelm M, Feelisch M, Spahr R, Piper H, Noack E, Schrader J . Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells. Biochem Biophys Res Commun. 1988; 154(1):236-44. DOI: 10.1016/0006-291x(88)90675-4. View

Pelckmans P, Boeckxstaens G, Van Maercke Y, Herman A, Verbeuren T . Acetylcholine is an indirect inhibitory transmitter in the canine ileocolonic junction. Eur J Pharmacol. 1989; 170(3):235-42. DOI: 10.1016/0014-2999(89)90544-x. View

Gillespie J, Sheng H . The effects of pyrogallol and hydroquinone on the response to NANC nerve stimulation in the rat anococcygeus and the bovine retractor penis muscles. Br J Pharmacol. 1990; 99(1):194-6. PMC: 1917525. DOI: 10.1111/j.1476-5381.1990.tb14677.x. View

Myers P, Minor Jr R, Guerra Jr R, Bates J, Harrison D . Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature. 1990; 345(6271):161-3. DOI: 10.1038/345161a0. View

Bult H, Boeckxstaens G, Pelckmans P, Jordaens F, Van Maercke Y, Herman A . Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990; 345(6273):346-7. DOI: 10.1038/345346a0. View

Kowaluk E, Fung H . Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J Pharmacol Exp Ther. 1990; 255(3):1256-64. View

Boeckxstaens G, Pelckmans P, Bult H, DE Man J, Herman A, Van Maercke Y . Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction. Eur J Pharmacol. 1990; 190(1-2):239-46. DOI: 10.1016/0014-2999(90)94132-h. View

Boeckxstaens G, Pelckmans P, Ruytjens I, Bult H, DE Man J, Herman A . Bioassay of nitric oxide released upon stimulation of non-adrenergic non-cholinergic nerves in the canine ileocolonic junction. Br J Pharmacol. 1991; 103(1):1085-91. PMC: 1908082. DOI: 10.1111/j.1476-5381.1991.tb12304.x. View

10.

Thornbury K, Ward S, Dalziel H, Carl A, Westfall D, Sanders K . Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon. Am J Physiol. 1991; 261(3 Pt 1):G553-7. DOI: 10.1152/ajpgi.1991.261.3.G553. View

11.

Hobbs A, Tucker J, Gibson A . Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non-vascular smooth muscle: role of superoxide anions. Br J Pharmacol. 1991; 104(3):645-50. PMC: 1908243. DOI: 10.1111/j.1476-5381.1991.tb12483.x. View

12.

Sanders K, Ward S . Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol. 1992; 262(3 Pt 1):G379-92. DOI: 10.1152/ajpgi.1992.262.3.G379. View

13.

Knudsen M, Svane D, Tottrup A . Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter. Am J Physiol. 1992; 262(5 Pt 1):G840-6. DOI: 10.1152/ajpgi.1992.262.5.G840. View

14.

Kerr S, Buchanan L, Bunting S, Mathews W . Evidence that S-nitrosothiols are responsible for the smooth muscle relaxing activity of the bovine retractor penis inhibitory factor. J Pharmacol Exp Ther. 1992; 263(1):285-92. View

15.

Stark M, Szurszewski J . Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology. 1992; 103(6):1928-49. DOI: 10.1016/0016-5085(92)91454-c. View

16.

Gibson A, Babbedge R, Brave S, Hart S, Hobbs A, Tucker J . An investigation of some S-nitrosothiols, and of hydroxy-arginine, on the mouse anococcygeus. Br J Pharmacol. 1992; 107(3):715-21. PMC: 1907768. DOI: 10.1111/j.1476-5381.1992.tb14512.x. View

17.

Rajanayagam M, Li C, Rand M . Differential effects of hydroxocobalamin on NO-mediated relaxations in rat aorta and anococcygeus muscle. Br J Pharmacol. 1993; 108(1):3-5. PMC: 1907706. DOI: 10.1111/j.1476-5381.1993.tb13429.x. View

18.

Kitamura K, Lian Q, Carl A, Kuriyama H . S-nitrosocysteine, but not sodium nitroprusside, produces apamin-sensitive hyperpolarization in rat gastric fundus. Br J Pharmacol. 1993; 109(2):415-23. PMC: 2175683. DOI: 10.1111/j.1476-5381.1993.tb13585.x. View

19.

Rand M, Li C . Differential effects of hydroxocobalamin on relaxations induced by nitrosothiols in rat aorta and anococcygeus muscle. Eur J Pharmacol. 1993; 241(2-3):249-54. DOI: 10.1016/0014-2999(93)90210-9. View

20.

Mathews W, Kerr S . Biological activity of S-nitrosothiols: the role of nitric oxide. J Pharmacol Exp Ther. 1993; 267(3):1529-37. View