Effects of hCGRP I and II on gastric blood flow and acid secretion in anesthetized rabbits

Bauerfeind, Peter; Hof, Robert P.; Hof, Akiko; Cucala, Mercedes; Siegrist, Sylvie; Ritter, Christoph von; Ja, Fischer

doi:10.1152/ajpgi.1989.256.1.g145

Cited by 26 publications

(33 citation statements)

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“…It will therefore be necessary in future studies to determine if this mucosal vasodilatation or any mediator release is a direct effect of ET-1 in the gastric microcirculation, perhaps through activation of ETB or other ET receptors (Masaki et al, 1991) or if it occurs secondarily to microvascular injury induced by Local intra-arterial infusion of a-CGRP induced a significant increase in gastric mucosal LDF. This agrees with previous reports where a-CGRP was found to be a potent vasodilator in the gastric microcirculation, determined by use of a variety of techniques including laser Doppler flowmetry and hydrogen gas clearance (Dipette et al, 1987;Bauerfeund et al,1989;Li et al, 1991;. Intravenous infusion of a-CGRP can reverse the vasoconstrictor action of ET-1 on the internal carotid vascular bed in the rat (Gardiner et al, 1990), and local a-CGRP administration reduces the vasoconstriction induced by ET-1 in rabbit skin (Brain et al, 1988).…”

Section: Effect Of Ax-cgrp On Et-j-induced Mucosal Injurysupporting

confidence: 91%

The paradoxical vascular interactions between endothelin‐1 and calcitonin gene‐related peptide in the rat gastric mucosal microcirculation

López-Belmonte

Whittle

1993

British J Pharmacology

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The interactions between local intra‐arterial infusion of endothelin‐1 (ET‐1) and rat α‐calcitonin gene‐related peptide (α‐CGRP) on gastric mucosal damage and blood flow have been investigated in the pentobarbitone‐anaesthetized rat. Close‐arterial infusion of ET‐1 (2–200 pmol kg−1 min−1) induced a significant and dose‐dependent increase in gastric mucosal haemorrhagic injury. Close‐arterial infusion of the higher doses of ET‐1 (100 and 200 pmol kg−1 min−1) resulted in a biphasic effect on mucosal blood flow, as determined by laser Doppler flowmetry (LDF). This consisted of an initial transient increase followed by a pronounced and sustained fall in LDF. Local microvascular constriction may thus contribute to the mechanisms underlying the gastric injury induced by these higher doses of ET‐1. However, close‐arterial infusion of lower doses of ET‐1 (2–50 pmol kg−1 min−1), that also provoked substantial mucosal damage, induced only a sustained and significant mucosal hyperaemia, which may be secondary to microvascular injury. Concurrent close‐arterial administration of rat α‐CGRP (50 pmol kg−1 min−1) significantly inhibited the extent of gastric mucosal injury induced by ET‐1 (5 pmol kg−1 min−1). Furthermore, concurrent close‐arterial infusion of this dose of α‐CGRP, which itself increased mucosal LDF, significantly inhibited the hyperaemic response induced by close‐arterial infusion of ET‐1 (5 pmol kg−1 min−1). These results indicate a damaging action on the gastric mucosa by low doses of ET‐1 which is independent of local vasoconstriction, that may involve a direct injury of the microvascular endothelium. The protective action of α‐CGRP thus seems unlikely to be due to a local vasodilator effect but may reflect protective actions on the microvascular endothelium

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Section: Effect Of Ax-cgrp On Et-j-induced Mucosal Injurysupporting

confidence: 91%

The paradoxical vascular interactions between endothelin‐1 and calcitonin gene‐related peptide in the rat gastric mucosal microcirculation

López-Belmonte

Whittle

1993

British J Pharmacology

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“…It is the most powerful vasoactive substance known and it increases mucosal blood flow. 4,5) CGRP is known to coexist with tachykinins in the population of sensory neurons in humans. 6) Substance P is widely distributed in the central and peripheral nervous system and in the enteroendocrine cells of the gut 7) and it participates in the regulation of gastrointestinal motility, secretion, and blood flow.…”

mentioning

confidence: 99%

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Sato

Katagiri

Inoue

et al. 2004

Biological & Pharmaceutical Bulletin

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Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles and are gastroprotective. To determine whether the pharmacologic effects of Dai-kenchu-to (DKCT) on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of the DKCT on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of DKCT 7.5 g caused significant increases in plasma CGRP-IS at 40 min, and in substance P-IS levels at 20 and 60 min, compared with a placebo group. The present study may indicate that the pharmacologic action of DKCT is closely related to changes in CGRP-and substance P-IS levels.

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“…A parallel stimulation of gastric blood flow by human CGRP I and II in rabbits concomitant with increased pentagastrin-stimulated acid output with human CGRP I and inhibition with human CGRP II also points to differentiated regulatory functions of the two closely homologous neuropeptides (2).…”

Section: Resultsmentioning

confidence: 87%

Distinct hemodynamic and gastric effects of human CGRP I and II in man

et al. 1991

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Distinct hemodynamic and gastric effects of human CGRP I and H in man. PEPTIDES 12(6) [1347][1348][1349][1350][1351] 1991.--The human calcitonin gene-related peptides I and II (or ct and 13) (CGRP I and II) are encoded by two different genes, but they have 34 of the 37 amino acid residues in common. Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p<0.01), and the heart rate (p<0.05), and plasma renin activity and aldosterone secretion than human CGRP H (p<0.02). Inhibition of pentagastrin-stimulated gastric acid output, on the other hand, was only obtained with CGRP II. The separate effects of human CGRP I and I1 on the cardiovascular and gastric systems are presumably mediated by different receptors or receptor pathways recognized by the two closely related neuropeptides. AldosteroneCalcitonin gene-related peptide Gastric acid secretion Renin activity Vasodilatation HUMAN and rat calcitonin gene-related peptides I and II (or ct and 13) (CGRP I and II) differ in only 3 and 1 of the 37 amino acid residues, respectively (1,31). They are products of two separate genes. In man, the two genes are located on the same chromosome 11 and may have arisen by gene duplication (31). The relative expression of human CGRP I and II at the level of mRNA and mature peptides varies in different tissues (6,15,28, 34,35). CGRP exerts profound effects on the cardiovascular system of man and experimental animals, which include vasodilatation, positive chronotropic and ionotropic actions on the heart, and stimulation of plasma renin activity (5, 9-11, 20, 32). The latter effect represents a counterregulatory mechanism to the hypotension evoked by CGRP, but CGRP also directly stimulated the release of renin from juxtaglomerular cells (20). CGRP, moreover, inhibits gastric acid secretion with unchanged mucosal blood flow (19,22,23,33). We have reported earlier that human CGRP II, unlike CGRP I, inhibits pentagastrin-stimulated acid output (3).To address other potentially different biological targets of human CGRP I and II, we have now compared the cardiovascular effects of the two CGRPs, and have reexamined the inhibition of gastric acid output. The results provide evidence that human CGRP I more potently stimulates blood flow in the skin and the common carotid artery, and plasma renin activity and aldosterone levels than CGRP II, but does not suppress gastric acid secretion.1Requests for reprints should be addressed to Dr. J. A. Fischer, Klinik METHOD PeptidesSynthetic human CGRP I and II (or a and 13) were purchased from Peninsula Laboratories (Belmont, CA). Over 95% of the immunoreactive material eluted as a single peak on reversedphase HPLC (28). The CGRP was dissolved in 0.15 M NaC1 containing 0.1% human serum albumin, and vials containing 6.6 nmol/ml were prepared under aseptic conditions by the University of Basel Hospital Pharmacy and were stored at -20°C. The concentration of CGRP peptides obtained by weighing and by radioimmunoassay was within 10% of the predicted values.Pentagastrin (Pep...

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Effects of hCGRP I and II on gastric blood flow and acid secretion in anesthetized rabbits

Cited by 26 publications

References 0 publications

The paradoxical vascular interactions between endothelin‐1 and calcitonin gene‐related peptide in the rat gastric mucosal microcirculation

The paradoxical vascular interactions between endothelin‐1 and calcitonin gene‐related peptide in the rat gastric mucosal microcirculation

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Distinct hemodynamic and gastric effects of human CGRP I and II in man

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