Involvement of cyclic GMP in non‐adrenergic, non‐cholinergic inhibitory neurotransmission in dog proximal colon

Ward, Sean M.; Dalziel, H. H.; Bradley, Michael E.; Buxton, Iain L. O.; Keef, Kathleen D.; Westfall, David P.; Sanders, Kenton M.

doi:10.1111/j.1476-5381.1992.tb13409.x

Cited by 92 publications

(73 citation statements)

References 38 publications

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“…The resulting solution was neutralized and kept on ice in an airtight container for the remainder of the day; solutions were prepared daily. Control experiments employing addition of vehicle or direct addition of NO (by addition of NO saturated water; see Ward et al, 1992) verified that the effect of CysNO was due to the delivery of NO.…”

Section: Preparation Of the Nitric Oxide Donor Cysnomentioning

confidence: 88%

“…Although nitric oxide (NO) has been found to play a role in the regulation of vascular (Furchgott & Zawadzki, 1980;Palmer et al, 1987) and nonvascular (Ward et al, 1992;Kannan & Johnson, 1992;Thornbury et al, 1992) smooth muscle tone, inhibition of platelet aggregation (Azuma et al, 1986), and the mediation of some immunological responses (Moncada et al, 1991), its role in the control of uterine smooth muscle contractility has yet to be fully characterized. Studies have been performed in the rat (Papka & McNeill, 1992;Shew et al, 1993;Natuzzi et al, 1993;Izumi et al, 1993;Conrad et al, 1993;Yallampalli et al, 1993;Franchi et al, 1994), guinea-pig (Weiner et al, 1994), human subjects (Izumi et al, 1993;Telfer et al, 1995;Buhimschi et al, 1995) and rabbit (Sladek et al, 1993) which suggest that the uterus is an NOproducing organ.…”

Section: Introductionmentioning

confidence: 99%

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Cyclic GMP‐independent effects of nitric oxide on guinea‐pig uterine contractility

Kuenzli

Bradley

Buxton

1996

British J Pharmacology

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1 The role of nitric oxide (NO) in the regulation of uterine contractility has yet to be clearly defined. We evaluated the effect of NO (in the form of S-nitroso-L-cysteine, CysNO) upon uterine contractility and guanosine 3',5'-cyclic monophosphate (cyclic GMP) accumulation in pregnant and nonpregnant guinea-pig myometrium.2 While CysNO had no effect upon spontaneous contractile activity in either pregnant or nonpregnant uterine tissues, addition of CysNO resulted in an immediate and reversible relaxation of oxytocin-or acetylcholine (ACh)-evoked contractions. 3 Relaxation of agonist-evoked contractions in response to CysNO was associated with significant elevations in intracellular cyclic GMP concentrations ([cyclic GMP]i). 4 Elevations in [cyclic GMP]j were not required for relaxation, as inhibition of guanylyl cyclase by methylene blue prevented [cyclic GMP]j accumulation while having no effect upon the ability of CysNO to relax agonist-evoked contractions. 5 Addition of the cyclic GMP-analogues, 8-Br-cyclic GMP and PET-cyclic GMP, only at high concentrations, produced partial relaxation of agonist-contracted tissues, suggesting the possibility that cyclic GMP may be sufficient but not necessary for myometrial relaxation. 6 Our studies not only provide evidence for a functional role for NO-modulation of agonist-evoked contractions in the pregnant and nonpregnant guinea-pig uterus, but also that these occur by a mechanism which is not dependent upon guanylyl cyclase activity.

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Section: Preparation Of the Nitric Oxide Donor Cysnomentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Cyclic GMP‐independent effects of nitric oxide on guinea‐pig uterine contractility

Kuenzli

Bradley

Buxton

1996

British J Pharmacology

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“…These observations indicate that the rapid relaxation in response to vagal stimulation was mediated by the release of NO. Methylene Blue has been reported to be a selective inhibitor of soluble guanylate cyclase, the proposed site of action of NO (Ward et al 1992;Chakder & Rattan, 1993). Baccari et al (1992) demonstrated that in the atropine-and guanethidinetreated animals, vagally mediated rebound contraction was depressed by prostaglandin synthesis inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Vagal control of nitric oxide and vasoactive intestinal polypeptide release in the regulation of gastric relaxation in rat.

Takahashi

Owyang

1995

The Journal of Physiology

128

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1. Gastric motility and neurotransmitter release in response to vagal stimulation were studied using a vascularly isolated perfused rat stomach. Gastric motor responses were recorded by a strain gauge force transducer implanted on the proximal stomach. 2. Electrical stimulation of vagal trunk (0-5-20 Hz) produced a triphasic response which was composed of a rapid transient relaxation (first phase) followed by a phasic contraction (second phase) and a delayed prolonged relaxation (third phase). Maximum responses of the first, second and third phase were observed at 2-5, 5 and 10 Hz, respectively. Intra-arterial infusion of tetrodotoxin (0-1 /LM) or hexamethonium (100 /M) completely abolished the triphasic response.3. The nitric oxide (NO) biosynthesis inhibitor NG-nitro-L-arginine (L-NNA; 100 ZM) significantly antagonized the rapid relaxation but had no effect on the delayed relaxation, while vasoactive intestinal polypeptide (VIP) antagonist (1 /M) significantly reduced the delayed relaxation without affecting the rapid relaxation. 4. In response to vagal stimulation, NO production ([3H]citrulline formation in gastric tissue preloaded with [3H]arginine) was maximum at 2-5 Hz, whereas VIP release into the venous effluent was largest at 10 Hz. Hexamethonium abolished vagal-stimulated NO production and VIP release. L-NNA had no effect on VIP release in response to vagal stimulation. 5. The nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperizinium (DMPP; 100 UM) also caused a triphasic response similar to that observed with vagal stimulation and produced a significant increase in VIP and NO formation. DMPP-evoked VIP release was not affected by L-NNA. Similarly, DMPP-evoked NO production was not antagonized by VIP antagonist.6. These results suggest that vagus nerve stimulation evokes NO and VIP release via nicotinic synapses which cause different modes of relaxation of the stomach. There is no interaction between NO and VIP release in response to vagal stimulation.

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“…62,127,[191][192][193][194][195][196][197] Numerous studies have shown responses to NO in the GI tract depend upon the production of cyclic GMP (cGMP) by soluble guanylate cyclase. [198][199][200] Guanylate cyclase is a heterodimer comprised of 2 subunits, α and β. Using immunohistochemistry Iino et al 182,201 showed that both subunits are strongly expressed in ICC but not resolved in smooth muscle.…”

Section: Functional Evidence Demonstrating the Importance Of Interstimentioning

confidence: 99%

The Significance of Interstitial Cells in Neurogastroenterology

Blair¹,

Rhee²,

Sanders³

et al. 2014

J Neurogastroenterol Motil

116

111

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Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα + cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.

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Involvement of cyclic GMP in non‐adrenergic, non‐cholinergic inhibitory neurotransmission in dog proximal colon

Cited by 92 publications

References 38 publications

Cyclic GMP‐independent effects of nitric oxide on guinea‐pig uterine contractility

Cyclic GMP‐independent effects of nitric oxide on guinea‐pig uterine contractility

Vagal control of nitric oxide and vasoactive intestinal polypeptide release in the regulation of gastric relaxation in rat.

The Significance of Interstitial Cells in Neurogastroenterology

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