Comparison of helodermin, VIP and PHI in pancreatic secretion and blood flow in dogs

Konturek, Stanisław J.; Yanaihara, Noboru; Pawlik, Wiesław W.; Jaworek, Jolanta; Szewczyk, Krystyna

doi:10.1016/0167-0115(89)90234-6

Cited by 14 publications

(5 citation statements)

References 15 publications

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“…Although an effect on neurotransmission has not been specifically ascribed to the eNOS isoform, this potential role is conceivable on the basis of evidence that eNOS has been detected in central nervous system (CNS) neural cells (8), that eNOS-derived NO may play a role as a retrograde neurotransmitter in the CNS (19), and that NO arising from nonneural eNOS-containing cells may diffuse freely between cells to act directly on intracellular targets (27). Without specifically implicating eNOS (or nNOS), the role of NOS in neurotransmission rather than vasodilation was examined by Holst et al (13), who showed that NOS inhibition reduces vagal-stimulated pancreatic protein secretion in pigs without affecting vasodilatation, which was attributed to the effects of VIP, a hormone with potent effects on PMBF and weak activity as a secretagogue (26). In addition, Klein et al (21) showed that truncal vagotomy in dogs reduced secretin-stimulated in vivo pancreatic secretion without altering PMBF.…”

Section: Discussionmentioning

confidence: 98%

Secretagogue-stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in mice

DiMagno¹,

Hao²,

Tsunoda³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Nitric oxide (NO) and NO synthase (NOS) play controversial roles in pancreatic secretion. NOS inhibition reduces CCK-stimulated in vivo pancreatic secretion, but it is unclear which NOS isoform is responsible, because NOS inhibitors lack specificity and three NOS isoforms exist: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). Mice having individual NOS gene deletions were used to clarify the NOS species and cellular interactions influencing pancreatic secretion. In vivo secretion was performed in anesthetized mice by collecting extraduodenal pancreatic duct juice and measuring protein output. Nonselective NOS blockade was induced with N(omega)-nitro-L-arginine (L-NNA; 10 mg/kg). In vivo pancreatic secretion was maximal at 160 pmol.kg(-1).h(-1) CCK octapeptide (CCK-8) and was reduced by NOS blockade (45%) and eNOS deletion (44%). Secretion was unaffected by iNOS deletion but was increased by nNOS deletion (91%). To determine whether the influence of NOS on secretion involved nonacinar events, in vitro CCK-8-stimulated secretion of amylase from isolated acini was studied and found to be unaltered by NOS blockade and eNOS deletion. Influence of NOS on in vivo secretion was further examined with carbachol. Protein secretion, which was maximal at 100 nmol.kg(-1).h(-1) carbachol, was reduced by NOS blockade and eNOS deletion but unaffected by nNOS deletion. NOS blockade by L-NNA had no effect on carbachol-stimulated amylase secretion in vitro. Thus constitutive NOS isoforms can exert opposite effects on in vivo pancreatic secretion. eNOS likely plays a dominant role, because eNOS deletion mimics NOS blockade by inhibiting CCK-8 and carbachol-stimulated secretion, whereas nNOS deletion augments CCK-8 but not carbachol-stimulated secretion.

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Section: Discussionmentioning

confidence: 98%

Secretagogue-stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in mice

DiMagno¹,

Hao²,

Tsunoda³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…This remarkable evolution of a multi-product gene is paralleled by the C-type natriuretic peptide gene in snakes, where the propeptide region has also been hypermutated to form multiple new post-translationally liberated toxin types, ranging from hypotensives to neurotoxins. Exendins, which are weaponised versions of the vasoactive intestinal peptides shown to reduce blood pressure and relax femoral arteries in rat and dog models, are currently known only from Heloderma venoms [ 24 , 162 , 163 , 164 ]. Goannatyrotoxin, currently known only from the varanid lizard V. glauerti , is a weaponised version of the pancreatic hormone peptide YY and produces a potent biphasic effect, characterised first by a sharp hypertension stage, followed by sustained hypotension [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

The Clot Thickens: Differential Coagulotoxic and Cardiotoxic Activities of Anguimorpha Lizard Venoms

Dobson,

Chowdhury,

Tai-A-Pin

et al. 2024

Toxins

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Despite their evolutionary novelty, lizard venoms are much less studied in comparison to the intense research on snake venoms. While the venoms of helodermatid lizards have long been assumed to be for defensive purposes, there is increasing evidence of toxic activities more useful for predation than defence (such as paralytic neurotoxicity). This study aimed to ascertain the effects of Heloderma, Lanthanotus, and Varanus lizard venoms on the coagulation and cardiovascular systems. Anticoagulant toxicity was demonstrated for the Varanus species studied, with the venoms prolonging clotting times in human and bird plasma due to the destructive cleavage of fibrinogen. In contrast, thromboelastographic analyses on human and bird plasmas in this study demonstrated a procoagulant bioactivity for Heloderma venoms. A previous study on Heloderma venom using factor-depleted plasmas as a proxy model suggested a procoagulant factor was present that activated either Factor XI or Factor XII, but could not ascertain the precise target. Our activation studies using purified zymogens confirmed FXII activation. Comparisons of neonate and adult H. exasperatum, revealed the neonates to be more potent in the ability to activate FXII, being more similar to the venom of the smaller species H. suspectum than the adult H. exasperatum. This suggests potent FXII activation a basal trait in the genus, present in the small bodied last common ancestor. This also indicates an ontogenetic difference in prey preferences in the larger Heloderma species paralleing the change in venom biochemistry. In addition, as birds lack Factor XII, the ability to clot avian plasma suggested an additional procoagulant site of action, which was revealed to be the activation of Factor VII, with H. horridum being the most potent. This study also examined the effects upon the cardiovascular system, including the liberation of kinins from kininogen, which contributes to hypotension induction. This form of toxicity was previously described for Heloderma venoms, and was revealed in this study was to also be a pathophysiological effect of Lanthanotus and Varanus venoms. This suggests that this toxic activity was present in the venom of the last common ancestor of the anguimorph lizards, which is consistent with kallikrein enzymes being a shared toxin trait. This study therefore uncovered novel actions of anguimorph lizard venoms, not only contributing to the evolutionary biology body of knowledge but also revealing novel activities to mine for drug design lead compounds.

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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%

“…Some biological actions of helodermin resemble those of VIP. Both peptides activate adenylate cyclase in plasma membranes of the rat pancreas but only helodermin induces amylase secretion (Konturek et al, 1989). 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).…”

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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Comparison of helodermin, VIP and PHI in pancreatic secretion and blood flow in dogs

Cited by 14 publications

References 15 publications

Secretagogue-stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in mice

Secretagogue-stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in mice

The Clot Thickens: Differential Coagulotoxic and Cardiotoxic Activities of Anguimorpha Lizard Venoms

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

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