Helodermin has a VIP-like effect upon canine blood flow

Naruse, Satoru; Yasui, Akihiro; Kishida, Satoshi; Kadowaki, Makoto; Hoshino, Minoru; Ozaki, Tsuyoshi; Robberecht, Patrick; Jamin, Christophe; Yanaihara, Chizuko; Yanaihara, Noboru

doi:10.1016/0196-9781(86)90192-0

Cited by 28 publications

(13 citation statements)

References 14 publications

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“…Envenomation by the Gila monster is not ordinarily fatal to adult humans, but results in intense pain, edema, weakness, and nausea associated with hypotension or tachycardia and can even cause anaphylactic shock or myocardial infarction (13)(14)(15)(16)(17). These signs and symptoms probably reflect powerful physiological effects of the kallikrein-like peptides and other bioactive peptides in Helo-omation (18,23). Previous reports have provided evidence for the existence of complex interactions between mast cells and VIP, in that mast cells can produce VIP (24,25) as well as express VIP receptors (26)(27)(28)(29) and degranulate in response to VIP (27,29), but mast cell-derived proteases can degrade VIP (30,31).…”

Section: Introductionmentioning

confidence: 99%

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

Akahoshi¹,

Song²,

Piliponsky³

et al. 2011

J. Clin. Invest.

133

131

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Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell-derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell-deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function.

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Section: Introductionmentioning

confidence: 99%

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

Akahoshi¹,

Song²,

Piliponsky³

et al. 2011

J. Clin. Invest.

133

131

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“…This more sustained action of helodermin on airway smooth muscle may reflect the greater resistance of this peptide to peptidase degradation, after binding to its receptor, due to its extended C-terminal region since VIP and other neuropeptides are readily degraded by neutral endopeptidases (Matsas et al, 1984). A synthetic variant of helodermin which lacked the C-terminal extension was also shown to lack the prolonged activity of the full-sequence peptide (Naruse et al, 1986). The protection of peptide activity by an extended C-terminal region may offer an attractive approach to the design of peptides for therapeutic use in respiratory disease such as asthma.…”

Section: Discussionmentioning

confidence: 99%

Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea‐pig lung parenchyma to histamine, acetylcholine and leukotriene D₄

Conroy

Samhoun

Piper

1991

British J Pharmacology

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The effect of vasoactive intestinal peptide (VIP) was studied on the contractile response of guinea‐pig lung parenchymal strips (GPP) induced by bronchoconstrictor agonists, such as leukotriene D4 (LTD4), histamine and acetylcholine (ACh). This effect of VIP was compared with helodermin, a peptide that is structurally related to VIP, and galanin, another neuropeptide that is thought to co‐exist with VIP. VIP (10 nm) induced a potent and reversible inhibition of the contractions of GPP induced by LTD4 (1–30 pmol) but did not affect those due to ACh (1–100 nmol) or histamine (1–30 nmol). A ten fold higher concentration of VIP (100 nm) did not further inhibit LTD4‐induced responses or reduce those induced by histamine or ACh. Helodermin (10 nm) had a similar inhibitory effect on contractions of GPP induced by LTD4 (3–30 pmol) but did not affect contractions induced by histamine (1–10 nmol). Indomethacin (2.8 μm) and salbutamol (10 nm) significantly reduced responses elicited by LTD4 and histamine but not those due to ACh. A ten fold higher concentration of salbutamol (100 nm) further inhibited the contractions due to LTD4 and histamine and at this concentration responses induced by ACh were inhibited. VIP (10 nm) and helodermin (10 nm) significantly reduced the LTD4‐induced release of thromboxane A2 (TXA2), measured as TxB2 by radioimmunoassay, from GPP. The smaller release of TxA2 induced by histamine was not significantly reduced in the presence of VIP. In comparative studies, galanin (10–100 nm) did not affect contractions of GPP induced by either LTD4, histamine or ACh. In contrast to VIP and helodermin, both at 0.1–3 nmol, which induced dose‐related relaxations of guinea‐pig trachea, galanin was inactive on this preparation in doses of up to 3 nmol. In conclusion, our results show that contractions of GPP induced by LTD4 are more sensitive to inhibition by VIP and helodermin than are contractions due to histamine or ACh. This inhibition appears to be associated with the different contribution of released TxA2 to contractions evoked by the agonists. VIP and helodermin inhibit the cyclo‐oxygenase‐dependent component of the LTD4‐induced response, as in the case of indomethacin.

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“…Helodermin-like peptides occur in high concentrations in the thyroid C cells and in the noradrenaline containing cells of the adrenal medulla in many mammals (Sundler et al, 1988;Grunditz et al, 1989;Bjartell et al, 1989). In the dog, intraarterial infusion of helodermin, like VIP, causes a dosedependent increase in femoral blood flow and intravenous injection produces systemic hypotension and tachycardia (Naruse et al, 1986;Konturek et al, 1989). In the present study, vascular effects of helodermin and the helospectins in the rat were compared to those of VIP on systemic blood pressure and on isolated distal femoral arteries.…”

Section: Introduction Methodsmentioning

confidence: 99%

Vascular effects of helodermin, helospectin I and helospectin II: a comparison with vasoactive intestinal peptide (VIP)

Grundemar

Högestätt

1990

British J Pharmacology

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1 Helodermin, helospectin I and helospectin II, peptides recently isolated from the salivary gland venom of Heloderma suspectum, were compared to vasoactive intestinal peptide (VIP) with respect to effects on systemic blood pressure and on isolated femoral arteries in the rat. 2 They all reduced blood pressure in a dose-dependent manner; helodermin was less effective than VIP. However, at doses higher than 1 nmol kg 1 all four peptides reduced blood pressure to about the same extent.3 The half-life of the hypotensive effect of VIP was longer than that of helodermin and the helospectins. 4 VIP and helodermin were equally potent in relaxing femoral arteries precontracted with phenylephrine or prostaglandin F2a.5 Helospectin I and II relaxed phenylephrine-contracted vessels to the same extent as VIP but with a lower potency. 6 Addition of VIP 1 M to preparations exposed to helodermin 1 gM or to either of the helospectins did not produce a further relaxation. 7 The findings indicate that VIP, helodermin and helospectin I and II have a similar profile of action and therefore may act on a common receptor.

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Helodermin has a VIP-like effect upon canine blood flow

Cited by 28 publications

References 14 publications

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea‐pig lung parenchyma to histamine, acetylcholine and leukotriene D₄

Vascular effects of helodermin, helospectin I and helospectin II: a comparison with vasoactive intestinal peptide (VIP)

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Helodermin has a VIP-like effect upon canine blood flow

Cited by 28 publications

References 14 publications

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea‐pig lung parenchyma to histamine, acetylcholine and leukotriene D4

Vascular effects of helodermin, helospectin I and helospectin II: a comparison with vasoactive intestinal peptide (VIP)

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Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea‐pig lung parenchyma to histamine, acetylcholine and leukotriene D₄