The role of calcitonin gene‐related peptide in gastric mucosal protection in the rat
TL;DR: The presence of circulating antibodies to calcitonin gene‐related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa, suggesting that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating Gastric mucosal defence mechanisms.
Abstract: The presence of circulating antibodies to calcitonin gene-related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa. Taken together with previous experimental and morphological data the results suggest that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating gastric mucosal defence mechanisms.
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TL;DR: The pathophysiological potential of the neural emergency system is best portrayed by the gastric hyperemic response to acid backdiffusion, which is signaled by afferent nerve fibers and creates favorable conditions for rapid restitution and healing of the wounded mucosa.
281 citations
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TL;DR: Investigations carried out in recent years have revealed that chilli or its active principle “capsaicin” is not the cause for ulcer formation but a “benefactor” which helps in prevention and healing of ulcers.
Abstract: In recent years, infection of the stomach with the organism Helicobacter Pylori has been found to be the main cause of gastric ulcers, one of the common ailments afflicting humans. Excessive acid secretion in the stomach, reduction in gastric mucosal blood flow, constant intake of non-steroid anti-inflammatory drugs (NSAIDS), ethanol, smoking, stress etc. are also considered responsible for ulcer formation. The prevalent notion among sections of population in this country and perhaps in others is that "red pepper" popularly known as "Chilli," a common spice consumed in excessive amounts leads to "gastric ulcers" in view of its irritant and likely acid secreting nature. Persons with ulcers are advised either to limit or avoid its use. However, investigations carried out in recent years have revealed that chilli or its active principle "capsaicin" is not the cause for ulcer formation but a "benefactor." Capsaicin does not stimulate but inhibits acid secretion, stimulates alkali, mucus secretions and particularly gastric mucosal blood flow which help in prevention and healing of ulcers. Capsaicin acts by stimulating afferent neurons in the stomach and signals for protection against injury causing agents. Epidemiologic surveys in Singapore have shown that gastric ulcers are three times more common in the "Chinese" than among Malaysians and Indians who are in the habit of consuming more chillis. Ulcers are common among people who are in the habit of taking NSAIDS and are infected with the organism "Helicobacter Pylori," responsible for excessive acid secretion and erosion of the mucosal layer. Eradication of the bacteria by antibiotic treatment and avoiding the NSAIDS eliminates ulcers and restores normal acid secretion.
94 citations
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TL;DR: The hypothesis that Substance P was the mediator of neurogenic inflammation was strengthened when it was shown that substance P caused vasodilatation and plasma extravasation and that this could be abolished by substance P antagonists and antibodies to substance P.
Abstract: In response to tissue injury or infection a complex series of homeostatic reactions involving the immune, circulatory and nervous systems occur, a response that is termed inflammation. In cutaneous tissues, the processes of inflammation lead to four well described clinical signs; heat, redness, edema and pain.I These are caused by vasodilatation, plasma extravasation and sensitization and activation of nociceptive C-fiber nerve endings.* The concept of neurogenic inflammation arose in the early twentieth century, based on the observation that antidromic stimulation of sensory nerves produced a cutaneous vasodilatation associated with an increase in vascular permeability, leading to extravasation of plasma protein^.^^^ In many investigations the sensory neurotoxin, capsaicin was used to show that a population of small diameter, chemosensitive, primary afferent nerve fibers gave rise to neurogenic inflammation (reviewed in refs. 4-6), culminating in Lembeck’s proposal that the undecapeptide, substance P was the chemical mediator of this response. 2 3 3 Substance P is a member of a family of peptides called the tachykinins.’ In mammals, this family consists of substance P, neurokinin A (NKA), neurokinin B (NKB) and two N-terminally extended forms of NKA, neuropeptide K and neuropeptide y. The precursors of the tachykinins are generated by two distinct genes, preprotachykinin (PPT) A and B. PPT-A can be alternatively spliced to encode for substance P alone, or substance P and the NKA products. The PPT-B gene encodes only NKB (reviewed in refs. 7-9).* The hypothesis that substance P was the mediator of neurogenic inflammation was strengthened when it was shown that substance P caused vasodilatation and plasma extravasation and that this could be abolished by substance P antagonists and antibodies to substance P.Io-l4 Moreover, the effect of antidromic stimulation was also abolished by these agents and, in addition, by capsaicin The site of action of substance
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TL;DR: It is concluded that acute Capsaicin administration protects against the ulcerative action of trinitrobenzene sulfonic acid, most likely via the release of protective neuropeptides from capsaicin-sensitive nerve endings.
66 citations
References
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TL;DR: Results indicate that capsaicin-sensitive afferent neurons are involved in gastric mucosal protection against ulcerogenic factors, and suggest that this type of gastric defense is primarily due to a local mechanism initiated by sensory nerve endings in the gastrics mucosa.
252 citations
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TL;DR: Data indicate that afferent nerve stimulation by intragastric capsaicin protects against deep mucosal damage in response to ethanol, an effect that seems related to an increase in mucosal blood flow but not to eicosanoid formation.
188 citations
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TL;DR: The results suggest that antibodies to calcitonin gene-related peptide are able to reduce the severity of the adjuvant arthritis syndrome, and that this peptide contributes to the inflammatory response seen in the later stages of the disease model.
38 citations
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TL;DR: Interactions between ET‐1 and sensory neuropeptides, which may reflect an important influence of these peptide mediators in the regulation of mucosal integrity, are suggested.
Abstract: 1. The interactions between endogenous and exogenous sensory neuropeptides on gastric mucosal injury induced by endothelin-1 (ET-1) have been investigated in the anaesthetized rat. 2. Close intra-arterial infusion of ET-1 (4-20 pmol kg-1 min-1) dose-dependently induced vasocongestion and haemorrhagic necrosis in the gastric mucosa. 3. Capsaicin-pretreatment, two weeks earlier to deplete sensory neuropeptides from primary afferent neurones, augmented the mucosal damage induced by ET-1, as assessed by both macroscopic and histological examination. 4. The damage induced by threshold doses of ET-1 alone or in capsaicin-pretreated rats was further enhanced by administration of indomethacin (5 mg kg-1, i.v.), indicating a modulatory influence of endogenous prostanoids. 5. Morphine administration (3 mg kg-1, i.v.), which can prevent neuropeptide release, augmented the damage induced by threshold doses of ET-1, this effect being reversed by naloxone (1 mg kg-1, i.v.). 6. Concurrent local intra-arterial infusion of rat alpha-calcitonin gene-related peptide (10-50 pmol kg-1 min-1) dose-dependently reduced the mucosal injury induced by ET-1. 7. These findings suggest interactions between ET-1 and sensory neuropeptides, which may reflect an important influence of these peptide mediators in the regulation of mucosal integrity.
30 citations