Participation of nitric oxide synthase and cyclo-oxygenase in the signal transduction pathway of ileal muscarinic acetylcholine receptors

Español, Alejandro; Sales, Marı́a Elena

doi:10.1006/phrs.2000.0723

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Intestinal problem spasm can be complementary related to the aggravated neuronal release of the neurotransmitter acetylcholine (Souza et al, 2013), furthermore experimental studies in vitro clearly demonstrated that acetylcholine acted such as a transmitter for the secreting enterocyte in the small intestine (Tobin et al, 2009). This parasympathetic neurotransmitter can be acted by two functions to regulating the physiological balance between contraction and relaxation in smooth muscle (Español and María, 2000). The contraction can be made by the activation of the M3 subtype, entraining release of inositol phosphate (IP3) by the activation of phospholipase C (PLC) on the other hand, the stimulation of the M2 receptor inhibit the adenylyl cyclase (AC) release entrained relaxation and maintaining of intestine tone (Sales et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Antispasmodic activity of Warionia saharae Benthem ex Benth. & Coss. on the rabbit and rat jejunums

Marghich¹,

Makrane²,

Alem³

et al. 2021

J Pharm Pharmacogn Res

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Context: Warionia saharae Benthem ex Benth. & Coss has been widely used for gastrointestinal problems in Morocco and Algeria. Aims: To explore the possible mechanism for its use to such ailments in order to rationalize some of these folkloric uses. We investigated the aqueous extract of this plant (AqWs) for antispasmodic activity on isolated rat and rabbit jejunums. Methods: To investigate the contractile activity of isolated jejunum preparations of rat and rabbit we had used in vitro techniques. Jejunums were suspended in tissue baths filled with KHB culture medium (37°C) and connected to force transducers. AqWs (0.1–3 mg/mL) was used with or without carbachol (10-6 M), KCl (25 mM), yohimbine (10-5 M), prazosin (10-5 M), propranolol (10-5 M), hexamethonium (10-4 M), atropine (10-6 M), methylene blue (10-5 M), L-NAME (10-4 M) and nifedipine (10-6 M). Results: AqWs at 0.1–3 mg/mL produced a relaxation on basal rabbit contractions with an IC50 = 1.55 ± 0.06 mg/mL. This effect was reversible and was not affected by pretreatment with the inhibitors of α and β adrenergic receptors yohimbine, prazosin and propranolol. The extract had an antispasmodic activity with an IC50 = 1.25 ± 0.02 mg/mL on rat jejunum precontracted with KCl rich medium (25 mM). This result suggests that the extract had a Ca2+ antagonist effect. This was fortified when pretreatment of the intestine with the extract induced a rightward shift in the Ca2+ concentration-response curves. AqWs exhibited also antispasmodic effect on carbachol (10-6 M)-induced contractions of rat jejunums with an IC50 = 1.53 ± 0.04 mg/mL. The extract at 3 mg/mL on rat jejunums pre-incubated with hexamethonium (10-4 M), atropine (10-6 M), and methylene blue (10-5 M), then contracted by KCl, decreased the maximum contraction but not totally like KCL alone without these inhibitors. For the jejunum pre-incubated with L-NAME (10-4 M), the spasmolytic effect of AqWs was comparable with KCL. Conclusions: These results suggest that the myorelaxant and antispasmodic effects are mediated possibly via Ca2+ antagonist, anticholinergic, and guanylate cyclase mechanisms but not by adrenergic and nitric oxide pathway.

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Section: Discussionmentioning

confidence: 99%

Antispasmodic activity of Warionia saharae Benthem ex Benth. & Coss. on the rabbit and rat jejunums

Marghich¹,

Makrane²,

Alem³

et al. 2021

J Pharm Pharmacogn Res

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“…In arterial smooth muscle, NOderived peroxynitrite was found to directly increase SERCA activity, resulting in a decreased intracellular Ca 2ϩ concentration and relaxation (37). In addition, peroxynitrite is known to stimulate prostaglandin H synthase and COX activity (38), and it has been shown that NO directly stimulates uterine (39) and ileal PGE 2 [prostaglandin (PG) E 2 ] production (40) to induce relaxation.…”

Section: Snp Effectsmentioning

confidence: 98%

Regulation of Spontaneous Contractile Activity in the Bovine Epididymal Duct by Cyclic Guanosine 5′-Monophosphate-Dependent Pathways

Mewe¹,

Bauer²,

Müller³

et al. 2006

Endocrinology

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Passage of spermatozoa through the epididymis is obligatory for sperm maturation processes and is based on spontaneous phasic contractions (SC) of the epididymal duct. Here, the functional role of cyclic GMP (cGMP) signaling in modulating SC in the bovine epididymal caput and corpus region was examined by muscle tension recording and immunological and autoradiographic techniques. The cGMP-analog 8-bromo (Br)-cGMP, as well as the nitric oxide (NO) donor sodium nitroprusside and the natriuretic peptides (NPs) atrial NP and C-type NP, displayed distally increasing SC-relaxant effects. In agreement, a distally increasing epididymal expression of the cGMP-dependent protein kinase I (PKG I), endothelial NO synthase (eNOS), and the atrial NP receptor was found. Immunoreactivity for PKG, soluble guanylate cyclase, and eNOS could be localized to the epididymal muscle cells as well as to the epithelial basal cells only at the corpus level. The SC-relevant action of NO and the NPs was cGMP dependent, and the action of 8-Br-cGMP, in turn, was modified by epithelial and luminal factors. The NOS inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) caused an increase in SC frequency, indicating basal activity of NO generating enzymes. The SC-inhibitory effect of 8-Br-cGMP was clearly reduced by the PKG inhibitor Rp-8-Br-cGMPS as well as by iberiotoxin, thapsigargin, and indomethacin, pointing to PKG as main SC-relevant target of cGMP, and to large-conductance calcium-activated K(+) channels, the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase and cyclooxygenase-1 as possible targets of PKG. These data support an essential role of cGMP signaling in the control of epididymal peristalsis, thereby enabling fine tuning of sperm transport and maturation.

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“…Therefore, NO and PGE2 are important to the osteogenic differentiation of MSCs induced by FSS. NO, a lipophilic molecule, can rapidly diffuse through biological membranes, activate guanylyl cyclase and promote cGMP synthesis (Espanol and Sales 2000). FSS-induced NO response is independent of FSS-induced PGE2 response in osteoblasts and osteocytes.…”

Section: No and Pge2mentioning

confidence: 99%

Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress

Liu

Yuan

Wang

2010

Biomech Model Mechanobiol

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Mechanical stimuli can improve bone function by promoting the proliferation and differentiation of bone cells and osteoblasts. As precursors of osteoblasts, human mesenchymal stem cells (hMSCs) are sensitive to mechanical stimuli. In recent years, fluid shear stress (FSS) has been widely used as a method of mechanical stimulation in bone tissue engineering to induce the osteogenic differentiation of hMSCs. However, the mechanism of this differentiation is not completely clear. Several signaling pathways are involved in the mechanotransduction of hMSCs responding to FSS, such as MAPK, NO/cGMP/PKG and Ca(2+) signaling pathway. Here, we briefly review how hMSCs respond to fluid flow stimuli and focus on the signal molecules involved in this mechanotransduction.

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Participation of nitric oxide synthase and cyclo-oxygenase in the signal transduction pathway of ileal muscarinic acetylcholine receptors

Cited by 7 publications

References 18 publications

Antispasmodic activity of Warionia saharae Benthem ex Benth. & Coss. on the rabbit and rat jejunums

Antispasmodic activity of Warionia saharae Benthem ex Benth. & Coss. on the rabbit and rat jejunums

Regulation of Spontaneous Contractile Activity in the Bovine Epididymal Duct by Cyclic Guanosine 5′-Monophosphate-Dependent Pathways

Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress

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