Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon

Thornbury, K. D.; Ward, Manus W.; Dalziel, H. H.; Carl, A.; Westfall, David P.; Sanders, Katherine

doi:10.1152/ajpgi.1991.261.3.g553

Cited by 85 publications

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“…In the present study we have found that non-cholinergic excitation occurs simultaneously with NANC inhibition at stimulus frequencies of 5 Hz and above. We have characterized noncholinergic neuronal responses for the first time in the absence of interference from NO, which appears to be the predominant enteric inhibitory transmitter in canine colonic muscles (see Thornbury et al, 1991;Ward et al, 1992b).…”

Section: Discussionmentioning

confidence: 99%

“…Noncholinergic excitatory input has usually been observed as a 'rebound' response following cessation of nerve stimulation, yet it is quite possible that the influence of non-cholinergic excitatory neurotransmission occurs throughout the period of stimulation. Since NO has been shown to mediate enteric inhibitory neurotransmission in the canine colon Thornbury et al, 1991;Ward et al, 1992b;Huizinga et al, 1992), this influence can be abolished by addition of arginine analogues that inhibit nitric oxide synthase . In the present study we have used a combination of atropine and arginine analogues to unmask and characterize non-cholinergic excitatory neural responses in the circular muscle of the proximal colon.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of nitric oxide synthesis reveals non‐cholinergic excitatory neurotransmission in the canine proximal colon

Shuttleworth

Sanders

Keef

1993

British J Pharmacology

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1 Neuromuscular transmission in the circular muscle of the canine proximal colon was examined, in the presence and absence of nitric oxide synthase inhibitors, by use of mechanical and intracellular microelectrode recording techniques. 2 Electrical field stimulation (EFS; 0.1-20 HZ) produced frequency-dependent contractions of circular muscle strips which reached a maximum at 15 Hz. These reponses were enhanced by NG-monomethyl-Larginine (L-NMMA; 300 AM) and reduced by atropine (1 JAM). The effects of L-NMMA were reversed by L-arginine (3 mM). All responses to EFS were abolished by tetrodotoxin (1 AM).3 In the presence of atropine, phentolamine and propranolol (all at 1 AM; 'non-adrenergic, noncholingergic (NANC) conditions'), EFS evoked frequency-dependent inhibition of phasic contractions which reached a maximum at 5 Hz. At higher frequencies of EFS, inhibition diminished, and these responses were followed by post-stimulus excitation.4 Under NANC conditions and in the presence of L-NG-nitroarginine methyl ester (L-NAME; 200 JAM), EFS evoked contractions at frequencies of 5 Hz or greater. These contractions were reduced by co-incubation with L-arginine (2 mM) and abolished by tetrodotoxin (I iAM). 5In the presence of atropine (1 JAM), EFS (5-20 Hz) caused frequency-dependent inhibition of electrical slow waves. In the presence of L-NAME (100 JAM) and atropine, the inhibitory response to EFS was abolished and an increase in slow wave duration was seen at stimulation frequencies greater than 5 Hz. The effects of EFS on slow wave duration were abolished by tetrodotoxin (1 JiM). 6 Atropine-resistant contractions to EFS were enhanced by indomethacin (10 iAM) and reduced or abolished by the non-selective NK,/NK2 tachykinin receptor antagonist D-Pro2, D-Trp7'9 SP, and by the selective NK2 receptor antagonist MEN 10,376 (10 AM). 7 Exogenous tachykinins mimicked non-cholinergic excitatory electrical and mechanical responses. The rank order of potency for contraction was neurokinin A>neurokinin B>substance P, suggesting a predominance of the NK2 sub-type of tachykinin receptors on colonic smooth muscle cells. Low concentrations of neurokinin A also increased the amplitude and duration of electrical slow waves. 8 These results suggest that: (i) in previous studies, non-cholinergic excitatory responses were masked by the simultaneous release of NO; (ii) non-cholinergic excitatory responses occur throughout the period of stimulation and are not manifest only as 'rebound' excitation; (iii) one or more tachykinins, possibly, acting via NK2 receptors, may mediate non-cholinergic excitatory responses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of nitric oxide synthesis reveals non‐cholinergic excitatory neurotransmission in the canine proximal colon

Shuttleworth

Sanders

Keef

1993

British J Pharmacology

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“…5 Some agents (e.g., those that increase cyclic AMP [cAMP] or cyclic GMP [cGMP]) induce relaxation by activating K + channels, inducing hyperpolarization and decreasing Ca 2+ influx. 6 - 7 2) Regulation of [Ca 2+ ]; independent of changes in membrane potential was termed "pharmacomechanical coupling." 4 There are several proposed mechanisms for pharmacomechanical coupling.…”

Section: Regulation Of Myoplasmic [Ca 2+ ]mentioning

confidence: 99%

Regulation of contraction and relaxation in arterial smooth muscle.

1992

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The phosphorylated myosin cyclically binds to actin filaments producing force or shortening, or both.3 This is the most widely accepted mechanism for the primary regulation of smooth muscle contraction. However, recent data suggest that the above regulatory scheme may be incomplete. In this review, I will discuss 1) the mechanisms regulating [Ca 2+ ],, 2) the mechanisms altering the dependence of myosin phosphorylation on [Ca 2+ ]i (i.e., the [Ca 2+ ] ; sensitivity of phosphorylation), and 3) the dependence of contractile force on myosin phosphorylation. Regulation of Myoplasmic [Ca 2+ ]Contractile stimuli affect [Ca 2+ ], by a number of mechanisms (see Figure 1): 1) Regulation of [Ca 2+ ]i by

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“…Another suggested Author for correspondence at: Department of Physiology 1, Karolinska Institutet, 171 77 Stockholm, Sweden endogenous compound is hydroxylamine or an analogue thereof (Thomas & Ramwell, 1989). If NO can be stored as a nitrosothiol compound in nerve-terminal vesicles it may be able to function as a classical neurotransmitter, stored and released from vesicles (Thornbury et al, 1991;. Cysteine is the most abundant source of free sulphydryl groups in mammalian tissue (Jocelyn, 1972), and at normal extracellular pH, CYSNO has a biological half-life similar to that of NO.…”

Section: Introductionmentioning

confidence: 99%

Smooth muscle relaxing effects of NO, nitrosothiols and a nerve‐induced relaxing factor released in guinea‐pig colon

Iversen

Gustafsson

Leone

et al. 1994

British J Pharmacology

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Institute, S-171 77 Stockholm, Sweden and **Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS 1 The aim of the present study was to compare the biological activity of S-nitroso-L-cysteine (CYSNO), S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and hydroxylamine to that of nitric oxide (NO) and a vascular relaxing factor released by nerve stimulation in the guinea-pig intestine. The biological activity was examined in a bioassay system with guinea-pig colon as donor tissue and a series of spiral strips of rabbit aorta without endothelium as detector tissues. 2 Electrical stimulation of the guinea-pig colon released a vascular relaxing factor. The half-life of the relaxing factor down the bioassay cascade was the same as exogenously applied NO. N0-nitro-L-arginine (L-NOARG) inhibited the release of bioactivity. 3 The relaxations of the assay tissues caused by exogenous CYSNO also declined during the passage down the cascade. However, in the presence of L-cysteine (10-5 M) the half-life of CYSNO increased and there was no significant breakdown through the cascade. In contrast, the half-life of applied NO and the vascular relaxing factor released by nerve stimulation was unaffected by the presence of L-cysteine. 4 Exogenously applied GSNO (20-50 nM), SNAP (2-4 nM) and hydroxylamine (300-600 nM) caused relaxations that did not decline during the passage down the cascade. 5 In summary, the relaxation of the bioassay tissues during nerve stimulation was indistinguishable from the relaxation induced by NO, whereas relaxations induced by CYSNO, GSNO, SNAP and hydroxylamine showed different pharmacological profiles. The released bioactivity is thus likely to be NO itself.

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Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon

Cited by 85 publications

References 0 publications

Inhibition of nitric oxide synthesis reveals non‐cholinergic excitatory neurotransmission in the canine proximal colon

Inhibition of nitric oxide synthesis reveals non‐cholinergic excitatory neurotransmission in the canine proximal colon

Regulation of contraction and relaxation in arterial smooth muscle.

Smooth muscle relaxing effects of NO, nitrosothiols and a nerve‐induced relaxing factor released in guinea‐pig colon

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