The Effects of Vasoactive Intestinal Polypeptide and of Adenosine 5′‐triphosphate on the Isolated Anococcygeus Muscle of the Mouse

Mirzazadeh

1989

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1 The effects of N-methylhydroxylamine (NMH) and of M&B 22948 on relaxations of the mouse anococcygeus to non-adrenergic, non-cholinergic (NANC) field stimulation and to a number of smooth muscle relaxant drugs were investigated. 2 Relaxations to NANC field stimulation (10Hz; 60s train) were reversibly blocked by NMH (1-5 mM), which also caused weak, transient reductions of carbachol (50 Mm)-induced tone. N,Ndimethylhydroxylamine (2 mM) and hydroxylamine (5 pM) reduced tone to the same extent as NMH, but neither produced any inhibition of NANC relaxations. 3 M&B 22948 tO M, which by itself reduced tone by 12%, potentiated submaximal but not maximal relaxations to NANC field stimulation; overall the log frequency-response curve was displaced to the left by a factor of 2.4 Sodium nitroprusside (0.01-1 gM), hydroxylamine (0.5-100 gM), and nitric oxide (2-200 pM) all relaxed carbachol-induced tone; relaxations to submaximal concentrations of these nitrovasodilators were reduced in the presence of 2 mm NMH, and potentiated in the presence of 1OMm M&B 22948. 5 Neither NMH (2 mM) nor M&B 22948 (10 Mm) affected relaxations induced by submaximal concentrations of vasoactive intestinal peptide (VIP; 1 M), papaverine (10MM), 3-isobutyl-1-methylxanthine (10MM), or 8-bromo-cyclic guanosine monophosphate (100Mm); relaxations to adenosine 5'-triphosphate (ATP, 2 mM) were unaffected by M&B 22948, but were potentiated by NMH. 6 The selective inhibition by NMH, and potentiation by M&B 22948, of NANC and nitrovasodilator-induced relaxations of the mouse anococcygeus suggests that the NANC transmitter is neither VIP nor ATP, but resembles the nitrovasodilator drugs in its mode of action. The NANC transmission system is therefore similar to that recently described in the bovine retractor penis.

Section: Resultsmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

N‐methylhydroxylamine inhibits and M&B 22948 potentiates relaxations of the mouse anococcygeus to non‐adrenergic, non‐cholinergic field stimulation and to nitrovasodilator drugs

Mirzazadeh

1989

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“…Haemoglobin reduced the responses to NO and the S-nitrosothiols, although it did not affect responses to IBMX. Previously, it has been shown that haemoglobin (in the form of haemolysed blood) inhibited NANC relaxations of the mouse anococcygeus without affecting those to VIP or ATP (Gibson & Tucker, 1982 (Hobbs et al, 1991). This and other observations (Gillespie & Sheng, 1989) have led to the proposal that NO may be released from the nerve attached to a carrier molecule, which protects it within the synaptic cleft.…”

Section: Discussionmentioning

confidence: 99%

An investigation of some S‐nitrosothiols, and of hydroxy‐arginine, on the mouse anococcygeus

Babbedge

Brave

et al. 1992

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1 The effect of five S-nitrosothiols, and of the stereoisomers of N0-hydroxy-arginine (HOARG), were investigated on the mouse anococcygeus. 2 All five S-nitrosothiols produced concentration-related (0.1-100IM) relaxations of carbachol (50 LM)-induced tone; the order of potency was S-nitroso-L-cysteine (CYSNO)> S-nitroso-N-acetyl-D,Lpenicillamine (SNAP)>S-nitrosoglutathione (GSNO)> S-nitrosocoenzyme A (CoASNO)> S-nitroso-N-acetyl-L-cysteine (NACNO). The relaxations were unaffected by the nitric oxide synthase (NOS) inhibitor, L-NG-nitro-arginine (10 JIM) (L-NOARG).3 Cold-storage of the tissue for 72 h resulted in loss of sympathetic and non-adrenergic, noncholinergic (NANC) nerve function. NOS activity in the tissue was reduced by 97%. Despite this, relaxations induced by the S-nitrosothiols were unaffected. 4 Haemoglobin (50 jM) attenuated relaxations induced by NO and the S-nitrosothiols, although responses to 3-isobutyl-1-methyl-xanthine were unaffected. N-methyl-hydroxylamine (2 mM) which has been shown previously to produce selective inhibition of NANC and nitrovasodilator responses in this tissue, also reduced responses to all S-nitrosothiols.5 Hydroquinone (100 gM) greatly reduced relaxations to CYSNO (by 88%) but had no effect on those to SNAP, GSNO, CoASNO or NACNO. Since hydroquinone does not reduce responses to NANC stimulation, CYSNO is unlikely to be the NANC transmitter. 6 L-HOARG by itself (up to 100 piM) had no significant effect on carbachol-induced tone or on NANC (10 Hz; 10 s train every 100 s) relaxations. However, it produced reversal of the inhibitory effects of L-NOARG (10;pM), being only slightly less potent than L-arginine. D-HOARG was without effect. L-HOARG had no effect on relaxations induced by 1.51iM NO. 7 The results show that S-nitrosothiols are potent relaxants of the mouse anococcygeus; they act directly on the smooth muscle with a mechanism similar to NO and other nitrovasodilators. In addition, the results are consistent with L-HOARG being an intermediate in the biosynthesis of NO from L-arginine, although there is no evidence for it acting to stabilize NO extracellularly.

“…During an investigation of the actions of putative inhibitory transmitters, excitation of these nerves by means of prolonged trains of field stimulation, caused a biphasic relaxation of the muscle (Gibson & Tucker, 1982). In this paper the results of some experiments carried out to characterize this phenomenon are detailed.…”

Section: Introductionmentioning

confidence: 99%

Biphasic non‐adrenergic, non‐cholinergic relaxations of the mouse anococcygeus muscle

1983

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1 Trains of field stimulation of 60 s duration caused a biphasic relaxation of carbachol (50 uM)-induced tone in the mouse anococcygeus. The optimal pulse frequency and width were 10 Hz and 1 ms respectively. 2 Tetrodotoxin (31, 124, and 310 nM) caused a dose-dependent reduction in the magnitude of both phases. Neither phase was affected by (±)-propranolol (1 pM), neostigmine (1 pM), (+)-tubocurarine (100 pM), or apamin (500 nM). Biphasic relaxations were observed in muscles from 6-hydroxydopamine pretreated mice. 3 Haemolysed blood (10, 40, and 100 pl/ml) reduced the magnitude of the first phase of nerve-induced relaxation to a greater extent than the second. This effect was reversible.4 Following a prolonged train of inhibitory nerve stimulation (10 Hz; 10 min) the magnitude of the first phase was reduced only slightly, but the second markedly. 5The possible relationships between the biphasic relaxation to field stimulation and putative non-adrenergic, non-cholinergic transmitters in the mouse anococcygeus are discussed.