Nitric oxide‐dependent and ‐independent hyperaemia due to calcitonin gene‐related peptide in the rat stomach

Holzer, Peter; Lippe, Irmgard Th.; Jocič, Milana; Wachter, C; Erb, R.E.; Heinemann, Ákos

doi:10.1111/j.1476-5381.1993.tb13824.x

Cited by 55 publications

(43 citation statements)

References 28 publications

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“…CGRP, as mentioned above, has a major role in the maintenance of gastric mucosal integrity via increasing mucosal blood flow partly directly by acting on vascular smooth muscle, partly indirectly, by releasing NO (Holzer et al, 1993) and somatostatin (Bunnett et al, 1990). As our result show, i.c.v., but not i.v.…”

Section: Discussionsupporting

confidence: 58%

Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats

Brancati

Zádori

Németh

et al. 2013

Brain Research Bulletin

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The aim of the present study was to analyze the potential role of substance P (SP) in gastric mucosal defense and to clarify the receptors and mechanisms, that may be involved in it. Gastric ulceration was induced by oral administration of acidified ethanol in male Wistar rats. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. We found that central (intracerebroventricular) injection of SP (9.3 -74 pmol) dosedependently inhibited the formation of ethanol-induced ulcers, while intravenously injected SP (0.37-7.4 nmol/kg) had no effect. The mucosal protective effect of SP was inhibited by pretreatment with neurokinin 1-, neurokinin 2-, neurokinin 3-and μ-opioid receptor antagonists, while δ-and κ-opioid receptor antagonists had no effect. Endomorphin-2 antiserum also antagonized the SP-induced mucosal protection. In the gastroprotective dose range SP failed to influence the gastric motor activity. Inhibition of muscarinic cholinergic receptors, or the synthesis of nitric oxide or prostaglandins significantly reduced the effect of SP. In addition, centrally injected SP reversed the ethanolinduced reduction of gastric mucosal CGRP content. It can be concluded, that SP may induce gastric mucosal protection initiated centrally. Its protective effect is likely to be mediated by endomorphin-2, and vagal nerve may convey the centrally initiated protection to the periphery, where both prostaglandins, nitric oxide and CGRP are involved in mediating this effect.

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Section: Discussionsupporting

confidence: 58%

Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats

Brancati

Zádori

Németh

et al. 2013

Brain Research Bulletin

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“…It follows that the hypertension caused by N°-nitro-L-arginine methyl ester cannot be held responsible for the concomitant Suppression of the ability of interleukin-1ß to facilitate the vasodilator response to capsaicin. The activity of N°-nitro-o-arginine methyl ester to elevate blood pressure, which has been noted previously (Holzer et al, 1993), is not understood at present. N°-nitro-L-arginine methyl ester was given systemically since this route of administration did not significantly diminish cutaneous blood flow, whereas local application of the drug has been observed to , reduce skin blood flow to a significant extent (Holzer and Jocic, 1994).…”

Section: Discussionmentioning

confidence: 93%

Nitric oxide mediates the amplification by interleukin-1β of neurogenic vasodilatation in the rat skin

Herbert¹,

Holzer²

1994

European Journal of Pharmacology

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Blood flow in the plantar hindpaw skin of anaesthetized ratswas measured by Iaser Doppler flowmetry. Intraplantar injection of interleukin-lß (50 pg) significantly enhanced the hyperaemic response to intraplantar capsaicin (0.3 ,.,.g). Pretreatment with a neurotoxic dose of capsaicin reduced the capsaicin-evoked hyperaemia and prevented the facilitatory effect of interleukin-lß. Blockade of nitric oxide formation by N°-nitro-L-arginine methyl ester failed to affect the capsaicin-evoked vasodilatation but abolished its amplification by interleukin-lß. These data indicate that the enhancement by interleukin-lß of the capsaicin-induced hyperaemia involves thin afferent nerve fibres and depends on nitric mdde as esse'ntial intermediate. lntroductionThe cutaneous vasodilatation induced by topical administration of capsaicin is to a large extent mediated by activation of thin afferent neiVe fibres and release of vasoactive peptides from their peripheral endings (Holzer, 1992). We have previously shown that the inflammatory cytokine interleukin-lß enhances the hyperaemia evoked by injection of capsaicin into the rat plantar hindpaw skin in a prostaglandin-dependent manner (Herbert and Holzer, 1994). Since the vasodilator effect of calcitonin gene-related peptide (CGRP), the major neuragenie mediator of the capsaicin-induced vasodilatation (Hughes and Brain, 1991;Brain et al., 1993), was not altered by interleukin-1ß it was concluded that the effect of the cytokine was brought about by sensitization of afferent neiVe endings to capsaicin (Herbert and Holzer, 1994).This inference was further tested here by examining the effect of interleukin-1/3 in rats in which thin afferent neurones bad been defunctionalized by systemic

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“…On the other hand, NO may be another EpDRF, since NO is also released from airway epithelium and relaxes airway smooth muscle (Dupuy et at., 1992;Filep et al, 1993). CGRP relaxes thoracic aorta and gastric microvasculatures by releasing NO (Gray & Marshall, 1992;Holzer et al, 1993). NO relaxes airway smooth muscle in vitro and in ivivo (Buga et al, 1989;Dupuy et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…It has a diverse spectrum of pharmacological activities, which include activity as a potent vasodilator (Brain et al, 1985). In vascular smooth muscle, CGRP causes vasodilatation via two separate mechanisms; endothelium-dependent and independent (Gray & Marshall, 1992;Holzer et al, 1993). When CGRP-induced vasodilatation is dependent on the presence of intact endothelium, it is usually inhibited by L-N0-nitro-arginine methyl ester (L-NAME), suggesting that this relaxation is caused via the release of nitric oxide (NO).…”

Section: Introductionmentioning

confidence: 99%

The effects of calcitonin gene‐related peptide on tracheal smooth muscle of guinea‐pigs in vitro

Ninomiya

Uchida

Endo

et al. 1996

British J Pharmacology

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1 The effect of calcitonin gene-related peptide (CGRP) on airway smooth muscle is controversial. The aim of this study was to determine whether the action of CGRP on tracheal strips of guinea-pigs is modulated by epithelium and whether this peptide-induced action involves other mediators including nitric oxide (NO) and endothelin (ET)-1.2 CGRP produced a weak dose-dependent increase in guinea-pig tracheal tension in vitro (-logEC50 = 8.5 ± 0.1, maximum contraction = 8.3 + 1.2% of 50 mM KCl-induced contraction, n = 6). In epitheliumdepleted preparations, CGRP (10'-M)-induced contraction was significantly potentiated from 9.0+1.9% to 41.1+6.0% (n=6).3 L-NG-nitro-arginine methyl ester (L-NAME, 10-4 M), which inhibits NO synthesis, enhanced the contractile response to CGRP from 9.0+1.9% to 31.2+1.1% (n=6). Indomethacin (10-5M) also enhanced the response to CGRP, although the effect was weak (13.4+3.2%, n=6). 4 Anti-ET-1 serum changed the CGRP-induced contraction into a relaxation. After incubation of the trachea with ET-1 (10-' M) to attenuate ET-1-induced responses, the CGRP-induced contraction also changed into a relaxation. BQ-123 (an ETA receptor antagonist) and BQ-788 (an ETB receptor antagonist) caused the same conversion of the CGRP response, from contraction to relaxation, although the relaxing effect elicited by BQ-788 was more potent than that by BQ-123. Maximum inhibitory responses were -31.0 + 3.3% and -13.0 + 2.3% of 50 mM KCl-induced contraction, respectively (n = 6). 5 In primary culture, guinea-pig tracheal epithelial cells released ET-1, and CGRP (10-5 M) significantly increased the release of ET-1. 6 These data suggest that the action of CGRP is modulated by airway epithelium and this mechanism involves the release of NO and ET-1. Especially, the majority of contractile action elicited by CGRP consists of an action of ET-1 via the predominant ETB receptor.

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Nitric oxide‐dependent and ‐independent hyperaemia due to calcitonin gene‐related peptide in the rat stomach

Cited by 55 publications

References 28 publications

Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats

Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats

Nitric oxide mediates the amplification by interleukin-1β of neurogenic vasodilatation in the rat skin

The effects of calcitonin gene‐related peptide on tracheal smooth muscle of guinea‐pigs in vitro

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