Effect of <tex>$Cu^{2+}$</tex> on relaxations to the nitrergic neurotransmitter, NO and S-nitrosothiols in the rat gastric fundusEffect of <tex>$Cu^{2+}$</tex> on relaxations to the nitrergic neurotransmitter, NO and S-nitrosothiols in the rat gastric fundus
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Research group
Laboratory Experimental Medicine and Pediatrics (LEMP)
Physiopharmacology (PHAR)
Publication type
Pharmacology. Therapy
Source (journal)
British journal of pharmacology. - London
119(1996):5, p. 990-996
Target language
English (eng)
University of Antwerp
1 The effects of addition of Cu2+ and chelation of Cu2+ were studied on relaxations in response to S-nitrosothiols and on relaxations to non-adrenergic non-cholinergic (NANC) nerve stimulation, nitric oxide (NO) and glyceryl trinitrate (GTN) in the rat gastric fundus. 2 The S-nitrosothiols S-nitroso-L-cysteine (NOCys, 1-300 nM), S-nitrosoglutathione (GSNO, 0.01-3 mu M) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 0.01-3 mu M) induced concentration-dependent relaxations of the rat gastric fundus muscle strip. The relaxant potencies of the S-nitrosothiols were NOCys>SNAP>GSNO. Relaxations to NOCys were transient and comparable to those to NANC nerve stimulation and NO whereas relaxations to GSNO and SNAP were sustained. The relaxations to NOCys, GSNO and SNAP were significantly and concentration-dependently enhanced by CuSO4 (330 mu M). The order of relaxant potency in the presence of CuSO4 was reversed to GSNO approximate to SNAP> NOCys. 3 In the presence but not in the absence of 0.1 mu M GSNO, CuSO4 (1 mu M) induced a rapid and transient relaxation which was inhibited by the superoxide radical generator, pyrogallol (30 mu M). CuCl2 but not FeSO4 mimicked the effect of CuSO4. 4 Electrical stimulation (0.5-8 Hz) of the rat gastric fundus strips induced frequency-dependent relaxations which were previously shown to be nitrergic in nature and which were not affected by CuSO4 (3-30 mu M). Relaxations to NO (3-100 nM) and GTN (0.01-1 mu M) were not affected by 3 and 10 mu M CuSO4 but were inhibited by 30 mu M CuSO4. 5 The Cu2+ chelator, bathocuproine (3-30 mu M) significantly and concentration-dependently inhibited the relaxations to NOCys (0.01-3 mu M), GSNO (0.01-10 mu M) and SNAP (0.01-3 mu M). The inhibitory effect of 10 mu M bathocuproine was reversed by 3 mu M CuSO4. 6 Bathocuproine (3-30 mu M) had no effect on the relaxations to NANC nerve stimulation (0.5-8 Hz) or on the concentration-response curve to NO (0.01-0.3 mu M), whereas relaxations to GTN (0.01-1 mu M) were significantly inhibited by 30 mu M bathocuproine. 7 From these results we conclude that relaxations to S-nitrosothiols and to nitrergic stimulation of the rat gastric fundus are differentially affected by addition and chelation of Cu2+, suggesting that the nitrergic NANC neurotransmitter in the rat gastric fundus is not an S-nitrosothiol but is more likely to be free nitric oxide.