Nitric oxide, and not vasoactive intestinal peptide, as the main neurotransmitter of vagally induced relaxation of the guinea pig stomach

Desai, Kaushik; Warner, Timothy D.; Bishop, Anne E.; Polak, Julia M.; Vane, John R.

doi:10.1111/j.1476-5381.1994.tb17124.x

Cited by 47 publications

(49 citation statements)

References 41 publications

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“…It seems unlikely that the effect is limited to control of a particular organ system. The dual excitatory (i.e., cholinergic) and inhibitory (i.e., noncholinergic, nonadrenergic) pathways of the vagus peripherally allow for excitation and/or inhibition of DMV neurons to lead to inhibition of smooth muscle (D'Amato et al, 1992;Grundy et al, 1993;Desai et al, 1994;Paterson et al, 2000). Unfortunately, no evidence exists to directly correlate morphological or electrophysiological properties of individual DMV neurons with their final effect on the viscera, so it is currently impossible to determine in a slice preparation which functional vagal pathway is affected by a given DMV neuron.…”

Section: Discussionmentioning

confidence: 99%

Vanilloid-Mediated Heterosynaptic Facilitation of Inhibitory Synaptic Input to Neurons of the Rat Dorsal Motor Nucleus of the Vagus

Derbenev

Monroe²,

Glatzer³

et al. 2006

J. Neurosci.

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Vanilloid type-1 receptors (VR1) are abundant in the dorsal vagal complex, where their function is mostly unknown. We examined the role of VR1 in regulating synaptic inputs to neurons of the dorsal motor nucleus of the vagus (DMV). Using patch-clamp recordings from DMV neurons in brainstem slices, capsaicin was found to increase action potential-independent inhibitory input onto DMV neurons. This rapid effect was mimicked by application of the endogenous cannabinoid, anandamide and blocked by VR1 antagonists. The VR1-mediated facilitation of synaptic inhibition was reduced by ionotropic and metabotropic glutamate receptor antagonists, suggesting an indirect, heterosynaptic enhancement of GABA release caused by a VR1-mediated increase in glutamate release from presynaptic terminals of excitatory neurons. Application of L-glutamate also increased GABA release. The paired-pulse ratio was increased for IPSCs evoked after electrical stimulation of the nucleus tractus solitarius, but the effect was slower than for the enhancement of spontaneous and miniature IPSCs. Capsaicin also increased the frequency of glutamatergic postsynaptic currents in a VR1-mediated manner. Results of these studies suggest that VR1-containing glutamatergic terminals contact DMV neurons. Activation of VR1 potently enhances glutamate release onto GABAergic terminals, facilitating GABA release. Endogenous cannabinoids can thereby rapidly enhance inhibitory input to DMV neurons via VR1-mediated presynaptic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Vanilloid-Mediated Heterosynaptic Facilitation of Inhibitory Synaptic Input to Neurons of the Rat Dorsal Motor Nucleus of the Vagus

Derbenev

Monroe²,

Glatzer³

et al. 2006

J. Neurosci.

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“…NO has been proposed to play many roles in the regulation of biological responses (11), and a definite role of NO in neural transmission has been strongly suggested (12,13). There is now evidence to support the idea that NO is a mediator of NANC relaxation in many parts of the gastrointestinal tract such as canine ileocolonic junction (13) and lower esophageal sphincter (14), rat gastric fundus (15,16), guinea pig stomach (17)(18)(19), and rat or mouse anococcygeus muscle (20,21). These NANC responses induced by electrical stimulation were definitely reduced by the NO synthase (NOS) inhibitor N°-nitro-Larginine (L-NNA), which indicates that NO is responsible for the inhibitory NANC transmission.…”

mentioning

confidence: 92%

“…Table 2. Effect of several autonomic drugs and NO related agents on NANC relaxations induced by EFS (5 Hz, 3.0 msec, 100 V, 10 sec trains) in the mouse whole stomach DISCUSSION Many reports have so-far concerned the role of NO in mediating NANC relaxation of isolated gastric smooth muscle in animal species such as rats (15,16), cats (23), dogs (24), guinea pigs (17)(18)(19) and ferrets (25). At present, however, no knowledge is available about the NANC inhibitory response in the mouse stomach.…”

Section: Effect Of Nos Inhibitors Hemoglobin and Methylene Blue On Tmentioning

confidence: 99%

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Pharmacological Features of Non-adrenergic Non-cholinergic (NANC) Relaxation Induced by Electrical Vagal Stimulation in Isolated Mouse Stomach

Yano

Kiyota

Yamamoto

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-Thenon-adrenergic non-cholinergic (NANC) relaxatory response in mouse isolated whole stomach was investigated by electrical vagal stimulation (EVS) to clarify whether nitric oxide (NO) mediates vagal NANC transmission. The stomach was mounted in an organ bath, and the intragastric pressure was measured. Dual electrodes were placed on the esophagus. In the presence of atropine, propranolol and phentolamine, EVS induced a marked gastric relaxation. The response was frequency-dependent, and reproducible by repeated stimulation. The response was blocked by hexamethonium and N°-nitro-L-arginine (L-NNA), a NO synthase inhibitor, and significantly depressed by methylene blue, a soluble guanylate cyclase inhibitor, but not by hemoglobin, a radical trapping agent. The inhibitory effect of L-NNA was reversed by L-arginine, a substrate for NO synthase, but not by D-arginine. Exogenous NO caused a relaxation that was inhibited by hemoglobin and methylene blue, but not by L-NNA. The electrical field stimulation also elicited a gastric relaxation that was inhibited by L-NNA and methylene blue, but not by hexamethonium and hemoglobin. These results suggest that the inhibitory NANC response to EVS in the mouse stomach is largely mediated by release of NO, and it is exclusively due to stimulation of vagal preganglionic neurons.

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“…Both vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) have been proposed as NANC neurotransmitters in the proximal part of the stomach (Lefebvre, 1993). Whereas in species such as the rat and the ferret, NO is mainly involved in short-lasting relaxations and in initiating sustained relaxations (Li & Rand, 1990;D'Amato et al, 1992;Grundy et al, 1993), in other species such as the guinea-pig it is also the predominant neurotransmitter during sustained relaxation (Lefebvre et al, 1992a;Desai et al, 1994). The vagal preganglionic e erent ®bres to the stomach seem centrally organized in a reciprocal manner: when the e erents supplying the intramural cholinergic neurones are active, the discharge in those supplying the intramural inhibitory NANC neurones is suppressed, and vice versa (Andrews, 1990).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the interaction between cholinergic and nitrergic neurotransmission in the pig gastric fundus

Leclere¹,

Lefebvre²

1998

British J Pharmacology

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1 The interaction between the cholinergic and nitrergic innervation was investigated in circular muscle strips of the pig gastric fundus. 2 In physiological salt solution containing 4610 76 M guanethidine, electrical ®eld stimulation (EFS; 40 V, 0.5 ms, 0.5 ± 32 Hz, 10 s at 4 min intervals) induced small transient relaxations at 0.5 ± 4 Hz, and large frequency-dependent contractions, sometimes followed by o -relaxations, at 8 ± 32 Hz. 3 In the presence of L-N G -nitroarginine methyl ester (L-NAME; 3610 74 M) or physostigmine (10 76 M), relaxations were reversed into contractions and contractions were enhanced. Physostigmine added to L-NAME further enhanced contractions, while addition of L-NAME to physostigmine had no additional e ect. O -relaxations were enhanced in the presence of L-NAME and physostigmine. L-NAME and physostigmine consistently increased basal tone. 4 Tissues contracted by 5-hydroxytryptamine or by acetylcholine responded to EFS in a similar way as in basal conditions and L-NAME reversed the relaxations at the lower stimulation frequencies into contractions and enhanced the contractions at the higher stimulation frequencies. 5 O -relaxations in the presence of L-NAME were partially reduced by a-chymotrypsin (10 U ml 71 ). 6 In the absence of physostigmine, the concentration-response curve to exogenous acetylcholine was not in¯uenced by L-NAME. 7 Contractions of the same amplitude induced by EFS at 4 Hz and by exogenous acetylcholine were either decreased or enhanced to the same extent by sodium nitroprusside (SNP; 10 75 M), depending upon the degree of relaxation by SNP. 8 These experiments suggest that endogenous nitric oxide interferes with cholinergic neurotransmission in the pig gastric fundus by functional antagonism at the postjunctional level. The interaction is independent of the degree of contraction.

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Nitric oxide, and not vasoactive intestinal peptide, as the main neurotransmitter of vagally induced relaxation of the guinea pig stomach

Cited by 47 publications

References 41 publications

Vanilloid-Mediated Heterosynaptic Facilitation of Inhibitory Synaptic Input to Neurons of the Rat Dorsal Motor Nucleus of the Vagus

Vanilloid-Mediated Heterosynaptic Facilitation of Inhibitory Synaptic Input to Neurons of the Rat Dorsal Motor Nucleus of the Vagus

Pharmacological Features of Non-adrenergic Non-cholinergic (NANC) Relaxation Induced by Electrical Vagal Stimulation in Isolated Mouse Stomach

Investigation of the interaction between cholinergic and nitrergic neurotransmission in the pig gastric fundus

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