PubMed Health⌕ Search

Biomedical subjects

S D Brain

Publications and source records attributed to S D Brain.

At least 73 records · Page 4Linked to original sources
PubMed1995

Essential role for nitric oxide in neurogenic inflammation in rat cutaneous microcirculation. Evidence for an endothelium-independent mechanism.

The possible modulatory role of nitric oxide (NO) in neurogenic edema formation in rat paw skin, induced by electrical stimulation of the saphenous nerve, was investigated by using two NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). Both L-NAME (100 mg/kg IV, P < .05) and 7-NI (10 mg/kg IV, P < .05) caused an L-arginine (100 mg/kg IV, P < .01)-reversible inhibition of neurogenic edema as measured by 125I-albumin accumulation, whereas D-NAME (inactive enantiomer of L-NAME) and 6-aminoindazole (structurally similar to 7-NI) were without inhibitory effect. L-NAME produced the predicted vasopressor effect (before, 115 +/- 18 mm Hg; 5 minutes after, 174 +/- 18 mm Hg; n = 6; P < .05), whereas 7-NI showed no significant increase in blood pressure (before, 96 +/- 9 mm Hg; 5 minutes after, 102 +/- 10 mm Hg; n = 6), and neither L-NAME nor 7-NI had any effect on basal or vasodilator calcitonin gene-related peptide (CGRP, 10 pmol per site)-stimulated local blood flow in rat skin, as measured by laser Doppler flowmetry. Furthermore, systemic and local 7-NI had no effect on edema formation induced by local administration of substance P (with or without CGRP) and histamine (with or without CGRP) in rat skin. Since 7-NI blocks edema produced by stimulation of the saphenous nerve, it is suggested that release of NO is involved in neurogenic edema formation, but the vasodilator action of NO is unimportant in this context.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of BQ-123 and Ro 47-0203 (bosentan) on endothelin-induced vasoconstriction in the rat skin.

The effectiveness of intradermal (i.d.) BQ-123 (cyclo[D-Asp-Pro-D-Val-Leu-D-Trp]) and i.d. Ro 47-0203 (bosentan, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyr imidin-4 - yl]-benzene-sulfonamide) has been evaluated on local microvascular responses to endothelin-1 and endothelin-3, measured by a multiple site 133Xe clearance technique in rat skin in vivo. Intradermal injection of endothelin-1 (0.3 pmol/site) and endothelin-3 (10 pmol/site) induced a similar (approximately 50-60%) decrease in basal blood flow in rat skin. BQ-123 (3-1000 pmol/site), a selective endothelin ETA receptor antagonist, caused a significant dose-dependent decrease in the vasoconstriction induced by endothelin-1 (P < 0.05) but was less effective on vasoconstriction induced by endothelin-3. Bosentan (3-1000 pmol/site), a new non-peptide mixed antagonist of endothelin ETA and endothelin ETB receptors, significantly reduced the vasoconstriction induced by endothelin-1 but was less effective than BQ-123. BQ-123 and bosentan were similarly effective as antagonists of endothelin-3. BQ-123 and bosentan had no effect on basal blood flow and no inhibitory activity on vasoconstriction induced by vasopressin (0.03 pmol/site) or phenylephrine (300 pmol/site). These findings indicate that BQ-123 and bosentan are effective and selective inhibitors of the vasoconstriction induced by endothelins in the rat skin microvasculature.

Animals↗
PubMed1994

Effect of a neurokinin-1 (NK1) receptor antagonist on oedema formation induced by tachykinins, carrageenin and an allergic response in guinea-pig skin.

The effect of the neurokinin-1 (NK1) receptor antagonist RP67580 in modulating inflammatory oedema formation has been investigated in guinea-pig skin. Oedema formation was measured over 30 min by the extravascular accumulation of intravenously-injected 125I-albumin in the anaesthetised guinea-pig. RP67580 was injected intradermally with the agents under test. Intradermal RP67580 (10 nmol/site) inhibits oedema formation induced by substance P (30 pmol) and neurokinin A (100 pmol), but not that induced by bradykinin (10-1000 pmol) or histamine (10 nmol). Substance P-induced oedema formation is similar in control (saline) and mepyramine (histamine H1 receptor antagonist) pretreated guinea-pigs suggesting a minimal involvement of histamine in substance P induced oedema formation in guinea-pig skin. Oedema formation induced by intradermal carrageenin (0.2%) was not inhibited by RP67580 (1-10 nmol). A significant but partial inhibition of oedema formation induced in a passive cutaneous anaphylaxis (PCA) response was observed. The oedema formation in the PCA was inhibited 50% by mepyramine pretreatment but in the presence of mepyramine no further inhibition of the PCA response by RP67580 was observed.

Animals↗
PubMed1994

Nitric oxide-dependent release of vasodilator quantities of calcitonin gene-related peptide from capsaicin-sensitive nerves in rabbit skin.

1. Calcitonin gene-related peptide (CGRP) is a potent and long lasting vasodilator in the cutaneous microvasculature of many species including the rabbit. In this study we have investigated the role of nitric oxide in the release of endogenous CGRP, in response to capsaicin, in rabbit skin. 2. Cutaneous blood flow was measured in response to intradermally-injected agents by a multiple site 133Xenon clearance technique. 3. The increased blood flow induced by capsaicin (100 nmol/site) and CGRP (3 pmol/site) was totally inhibited by the CGRP antagonist CGRP(8-37) (1 nmol/site), whilst the increased blood flow induced by sodium nitroprusside (0.3, 1 and 3 nmol/site) was unaffected by CGRP(8-37). 4. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 30 nmol/site) had no effect on the vasodilator response induced by CGRP, but significantly inhibited capsaicin-induced blood flow. The inhibitory effect of L-NAME on capsaicin-induced blood flow was reversed by intradermal L-arginine (300 nmol/site), whilst the inactive enantiomer D-NAME (30 nmol/site) and the alpha-adrenoceptor agonist phenylephrine (10 pmol/site), at a dose which had a similar effect to L-NAME on basal blood flow, had no effect on capsaicin-induced blood flow. 5. These results suggest that CGRP is the important vasodilator which is released from capsaicin-sensitive sensory nerves in rabbit skin and that the release of CGRP, but not its mechanism of vasodilator action, is nitric oxide-dependent in the rabbit cutaneous microvasculature.

Animals↗
PubMed1994

Inhibition by SR 140333 of NK1 tachykinin receptor-evoked, nitric oxide-dependent vasodilatation in the hamster cheek pouch microvasculature in vivo.

1. This study investigated tachykinin-evoked vasodilatation in the microvasculature of the hamster cheek pouch in vivo. Arterioles and venules were observed by intravital microscopy with video recording, and vasodilatation and constriction, defined as changes in blood vessel diameter, measured by image analysis. All agents were applied topically by superfusion. None of the agents tested had a significant effect on venule diameter. 2. When arterioles were preconstricted (by ca. 50%) with endothelin-1 present in the superfusing medium, substance P (0.3-30 nM) was a potent vasodilator, being 10 fold more active than both neurokinin A and the NK1 receptor-selective agonist, substance P methyl ester. The NK2 receptor-selective agonist, [beta-Ala8]-NKA(4-10)(0.1-10 microM) was active only at high concentrations, and the NK3 receptor-selective agonist senktide (0.1-10 microM) was virtually inactive (n = 8 hamsters). Dilatation evoked by tachykinins and analogues was rapid in onset (< 0.5 min) and readily reversible. 3. At low concentrations (1-10 nM), the non-peptide tachykinin NK1 receptor antagonist SR140333 ((S)1-(2-[3(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)pi peridin-3- yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octone, chloride) had no effect on the diameter of preconstricted arterioles per se, but potently inhibited dilator responses to substance P methyl ester (apparent pKB 9.9 +/- 0.2; n = 5 hamsters, n = 10 estimates). SR140333 (10 nM) did not inhibit submaximal dilator responses evoked by human alpha calcitonin gene-related peptide (alpha CGRPh; 1.0 nM; P > 0.05; n = 5). 4 The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 microM) caused a51.3 +/- 5.4% arteriolar constriction. In the presence of L-NAME, submaximal vasodilator responses to substance P (10-I00 nM) and carbachol (0.1-1.0 microM) were significantly attenuated (n = 5 hamsters;P<0.05) as compared to responses obtained in preparations that were preconstricted to a similar extent by endothelin-l (48.0 +/- 5.6%). L-NAME (10 M) was without effect on submaximal vasodilator responses to alpha CGRPh (0.1 nM) or sodium nitroprusside (1O nM) (n = 5 hamsters; P> 0.05).5 We conclude that tachykinin-evoked arteriolar vasodilatation in the hamster cheek pouch is mediated via NK, receptor activation and depends, at least in part, on the release of nitric oxide. The NKI receptors mediating vasodilatation can be blocked by topical application of SR140333; which may therefore be useful in the investigation of the role of NK1 receptors in neurogenic inflammation in the microvasculature.

Animals↗
PubMed1994

Vasodilator responses to calcitonin gene-related peptide (CGRP) and amylin in the rat isolated perfused kidney are mediated via CGRP1 receptors.

This study was designed to characterize the calcitonin gene-related peptide (CGRP) receptors mediating vasodilation in the rat isolated perfused kidney and to address the question as to whether amylin, a 37 amino acid peptide having about 50% overall sequence homology with CGRP, interacts with common CGRP receptors or acts via distinct amylin receptors. Human alpha-CGRP (h alpha CGRP) and human beta-CGRP, rat alpha-CGRP and rat amylin amide produced dose-related vasodilation of the perfused renal vascular bed with pD2 estimates of rat alpha-CGRP (10.8 +/- 0.2), h alpha CGRP (10.5 +/- 0.2), human beta-CGRP (10.5 +/- 0.2) and rat amylin amide (9.4 +/- 0.3). In contrast, the CGRP2 receptor-selective agonist [acetamidomethyl-cysteine2.7]h alpha CGRP (0.1 mumol) was inactive. The CGRP1-receptor antagonist, h alpha CGRP8-37 reversibly antagonized the vasodilator response induced by h alpha CGRP with an apparent pK1 of 8.03 +/- 0.21. The analog h alpha CGRP8-37 (1 microM) also reversibly inhibited submaximal responses to rat amylin amide. In contrast, rat amylin8-37 (1 microM) had no significant inhibitory effect either on rat amylin amide- or on h alpha CGRP-induced vasodilation (P > .05), showing that rat amylin8-37 does not have affinity for the CGRP1 receptor in this preparation. These data suggest that the predominant CGRP receptors in the rat renal vascular bed are of the CGRP1 type, and that the vasodilation induced by rat amylin amide is due to CGRP1 receptor activation.

Amyloid↗
PubMed1993

The effect of intra-articular capsaicin on passive synovial anaphylaxis and blood flow in the rat knee joint.

Normal rat and human synovium is innervated by small diameter, unmyelinated, peptide-containing nerves. A close anatomical association between these nerves and mast cells has been postulated23, although functional interactions have not been described. Capsaicin is frequently used to activate sensory nerves and we have examined both acute and long-term effects of capsaicin on passive synovial anaphylaxis (PSA) and blood flow in the rat knee joint. The acute injection of capsaicin into the synovial space (330 nmol, 30 min prior to antigen) significantly inhibited plasma extravasation into the joint tissues (measured by accumulation of [125I]-human serum albumin) following PSA, and produced vasoconstriction in normal joints (measured by 133Xe clearance). There was no effect on plasma extravasation when capsaicin was injected 3 h prior to antigen. Inhibition of the PSA response following acute intra-articular capsaicin was not reversed by pretreatment with the cyclo-oxygenase inhibitor indomethacin (to inhibit thromboxane generation) or in rats chronically treated with guanethidine (to deplete noradrenaline from post-ganglionic sympathetic fibres). Further, a longer term pre-treatment of the joints with a single intra-articular injection of capsaicin (3.3 mumol) also attenuated plasma extravasation following induction of PSA 7 days later, and was accompanied by a non-significant decrease in joint blood flow. Plasma extravasation in response to compound 48/80, a non-immunological mediator of mast-cell degranulation, was not affected in joints treated with capsaicin 7 days previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗
PubMed1993

Big endothelin-1 and big endothelin-3 are constrictor agents in the microvasculature: evidence for the local phosphoramidon-sensitive conversion of big endothelin-1.

The effect of local administration of big endothelin-1 (1-38, big ET-1) has been investigated on blood flow in the skin of anaesthetised rats, measured by 133Xe clearance. The local effects of big ET-1 and big endothelin-3 (1-41, big ET-3) have also been determined on microvessel diameter by intravital microscopy of the cheek pouch of anaesthetised hamsters. Big ET-1 (i.d.) caused a dose-dependent decrease in skin blood flow and was 10 times less potent than endothelin-1 (ET-1). Phosphoramidon (30 nmol/site i.d.) did not effect blood flow but when coinjected selectively attenuated the effect of big ET-1 (1 and 3 pmol/site, P < 0.05). In the cheek pouch big ET-1 (100 pmol) induced an intense and long-lasting arteriolar constriction. Phosphoramidon (100 nmol) abolished constriction to big ET-1 (100 pmol) but not to ET-1 (10 pmol). The modest constriction induced by big ET-3 (300 pmol) was not inhibited by phosphoramidon (100 nmol). Results suggest that a phosphoramidon-sensitive endothelin-converting enzyme situated close to microvascular vessels is important in the conversion of big ET-1. The mechanism for activity of big ET-3 in the microcirculation is unclear.

Animals↗
PubMed1993

The contribution of calcitonin gene-related peptide (CGRP) to neurogenic vasodilator responses.

The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator in the microcirculation of many tissues including the skin and joint. In order to elucidate the mechanism of endogenous CGRP release, we have used a multiple site 133Xe clearance technique to measure local blood flow changes in response to agents injected intradermally in the rabbit. Capsaicin (100 nmol/site) and human alpha CGRP (3 pmol/site) stimulated similar increases in blood flow and, in both cases, the effect was totally abolished by the CGRP antagonist, CGRP8-37 (1 nmol/site). By contrast, the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L-NAME, 30 nmol/site) had little effect on human alpha CGRP-induced vasodilation, but caused significant inhibition of the response to capsaicin (p < 0.05). These results show that increased blood flow in rabbit skin caused by exogenous CGRP is independent of nitric oxide. In addition, however, they suggest that nitric oxide is required for either the release of endogenous CGRP from capsaicin-sensitive nerves or its subsequent activity.

Animals↗
PubMed1993

Activation of tissue kallikrein-kininogen-kinin system in rabbit skin by a fraction isolated from Phoneutria nigriventer (armed spider) venom.

Phoneutria nigriventer venom was fractionated by gel filtration followed by ion-exchange chromatography from which 16 fractions (I-XVI) were obtained and assayed in rabbit skin in order to identify those responsible for the increased vascular permeability observed with the whole venom. The fractions, and control mediators (tissue kallikrein, bradykinin and histamine) were intradermally injected in male New Zealand white rabbits. Local oedema formation was measured as the local accumulation of i.v. injected 125I-human serum albumin into skin sites. Fraction XIII was the only fraction assayed which significantly induced oedema formation. Fraction XIII-induced oedema was greatly reduced by either the protease inhibitor aprotinin or the bradykinin B2 receptor antagonist D-Arg,[Hyp3,Thi5,8D-Phe7]-Bk, whereas the plasma kallikrein inhibitor soybean trypsin inhibitor failed to significantly affect this oedematogenic response. The kininase II inhibitor captopril markedly potentiated fraction XIII-induced oedema. Our results indicate that the increased vascular permeability induced by fraction XIII is due to local generation of kinins in response to tissue (but not plasma) kallikrein-kinin system activation.

Animals↗
PubMed1993

The modulation of inflammatory oedema by calcitonin gene-related peptide.

1. The effect of calcitonin gene-related peptide (CGRP) when given with or as a pretreatment to oedema inducing agents was investigated in the skin and paws of male Wistar and Sprague Dawley rats. 2. Oedema formation at intradermally-injected sites in the skin was measured by a 125I-labelled human serum albumin accumulation technique and paw oedema was measured by a weight displacement technique. 3. CGRP (30 pmol) when given with, or as a 20 min pretreatment, markedly potentiated oedema formation induced by substance P (100 pmol) in rat skin. In comparison, CGRP had little effect on 5-hydroxytryptamine (5-HT, 0.1-3 nmol)-induced oedema when given as a co-injection but significantly potentiated 5-HT-induced oedema when given as a 20 min pretreatment in the skin. Similar results were obtained in both Wistar and Sprague Dawley rats. 4. Pretreatment with CGRP (30 pmol) had little modulatory effect on oedema induced by substance P (100 pmol) in the presence of the vasodilator prostanoid, prostaglandin E1 (PGE1, 850 pmol) in the skin of Wistar rats. 5. Pretreatment with CGRP (30 pmol) caused a non-significant increase in carrageenin (300 micrograms)-induced oedema in the hind paw of Wistar rats. Capsaicin (100 nmol) given as a pretreatment had little effect on carrageenin-induced oedema. 6. CGRP (30 pmol), given as a pretreatment, had little modulatory effect on 5-HT (3 nmol)-induced oedema in the paw of Wistar rats but a non-significant decrease in paw oedema was observed in Sprague Dawley rats. 7. The results suggest that CGRP, either given together with .or as a pretreatment to mediators of increased microvascular permeability, depending on circumstance, can act in a synergistic manner to increase oedema formation. Little evidence was obtained for an anti-inflammatory effect of CGRP in either the rat skin or paw.

Alprostadil↗
PubMed1993

Activation by Phoneutria nigriventer (armed spider) venom of tissue kallikrein-kininogen-kinin system in rabbit skin in vivo.

1. The purpose of the present study was to investigate the mechanisms by which venom from Phoneutria nigriventer spider induces increases in vascular permeability in rabbit skin. 2. Local oedema formation, in response to intradermally-injected agents, was measured in male New Zealand white rabbits as the local accumulation of i.v. injected 125I-labelled human serum albumin into skin sites. 3. Phoneutria nigriventer venom (10-30 micrograms/site) increased vascular permeability, which was inhibited by trasylol (10 micrograms/site) and the bradykinin B2 receptor antagonists D-Arg,[Hyp3,Thi5,8,D-Phe7]-BK (3 nmol/site) and Hoe 140 (0.3 nmol/site). In addition, the oedema induced by the venom was potentiated by the kinase II inhibitor, captopril (1 nmol/site). The lipoxygenase inhibitor, BWA4C (10 nmol/site) and the PAF antagonist, WEB 2086 (100 nmol/site) had no effect on the venom-induced increase in vascular permeability. 4. Incubation of rabbit plasma with Phoneutria nigriventer venom in vitro did not cause bradykinin formation. Further, the plasma kallikrein inhibitor, soybean trypsin inhibitor (10 micrograms/site), had no effect on the venom-induced increase in vascular permeability in rabbit skin. 5. These results indicate that the oedema produced by Phoneutria nigriventer venom is dependent on the activation of the tissue kallikrein-kinin system.

Alprostadil↗
PubMed1993

Effect of a calcitonin gene-related peptide antagonist (CGRP8-37) on skin vasodilatation and oedema induced by stimulation of the rat saphenous nerve.

1. The effect of the calcitonin gene-related peptide antagonist (CGRP8-37, 400 nmol kg-1, i.v.) on the increased blood flow induced by calcitonin gene related peptide (CGRP), vasodilator prostaglandins, and topical capsaicin was measured with a laser Doppler blood flow meter in rat abdominal skin. 2. The saphenous nerve was electrically stimulated and the effect of CGRP8-37 (400 nmol kg-1, i.v.) on the increased blood flow (measured by laser Doppler flowmetry) and oedema formation (measured by the extravascular accumulation of [125I]-albumin) was investigated in the rat hind paw. 3. CGRP8-37 (400 nmol kg-1, i.v.) had no effect on basal cutaneous blood flow at uninjected sites and sites injected with Tyrode buffer, but acted selectively to inhibit the increased blood flow induced by intradermal CGRP (10 pmol/site, P < 0.05), but not that induced by prostaglandin E2 (PGE2, 300 pmol/site) or carba-prostacyclin (cPGI2, 100 pmol/site). 4. Capsaicin (0.1-33 mM), applied topically, acted in a dose-related manner to increase blood flow. CGRP8-37 (400 nmol kg-1, i.v.) almost totally inhibited blood flow induced by capsaicin (10 mM; P < 0.05) but did not significantly inhibit blood flow induced by a higher dose of capsaicin (33 mM). 5. The increased blood flow induced by short stimulation of the saphenous nerve (10 V, 1 ms, 2 Hz for 30 s) was inhibited by 76%, 5 min after i.v. CGRP8-37 (400 nmol kg-1, i.v., P < 0.05). 6. A longer (5 min) electrical stimulation of the saphenous nerve caused oedema formation, in addition to increased blood flow. The oedema formation was significantly inhibited by CGRP8-37 (400 nmol kg-1,i.v., P<0.05).7. The results suggest that the potent microvascular vasodilator neuropeptide, CGRP, is responsible for the increased blood flow observed after short stimulation of the saphenous nerve and that endogenous CGRP contributes in a pro-inflammatory manner to neurogenic oedema formation in the rat hind paw.

Alprostadil↗
PubMed1992

Olvanil: more potent than capsaicin at stimulating the efferent function of sensory nerves.

The capsaicin analogue olvanil stimulated an increase in cutaneous blood flow when injected intradermally into the anaesthetised rabbit, as measured using a 133Xenon clearance method. Olvanil was found to be a 10-fold more potent vasodilator (on a molar basis) than capsaicin. The effect of both vasodilators was significantly inhibited by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37). These findings suggest that olvanil stimulates the efferent function of cutaneous sensory nerves in a more potent manner than capsaicin. We therefore suggest that olvanil is a useful pharmacological tool for studying the activity of neuropeptides released from sensory nerves.

Anesthesia↗
PubMed1992

Evidence that calcitonin gene-related peptide contributes to inflammation in the skin and joint.

Calcitonin gene-related peptide produces dose-related vasodilatation after intradermal injection in several species. In the present study, CGRP increased blood flow in rabbit skin but had no direct effect on edema formation in rat or rabbit skin or in the rat knee joint. However, CGRP produced significant potentiation of edema formation when co-injected with histamine, a potent mediator of increased vascular permeability. Therefore, release of CGRP from stimulated C-fiber nerves may contribute to the vascular changes that are an integral part of the inflammatory process. The activity of the putative CGRP antagonist CGRP8-37 (300 pmol) against CGRP was also investigated in rabbit and rat skin. Whereas it was found to selectively antagonize the effects of CGRP in rabbit skin, the antagonist produced edema in rat skin at the same dose. Thus, CGRP8-37 may be used in the rabbit to study the effects of endogenously released CGRP, but caution is required when this antagonist is used in the rat.

Animals↗
PubMed1992

Human mast cell tryptase attenuates the vasodilator activity of calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP) is localized in and released from sensory nerves. It is a potent and long acting vasodilator which has been suggested to play a role in the control of blood flow. Using HPLC and trichloroacetic acid precipitation techniques, we have examined the ability of human mast cell lysates and a purified preparation of mast cell tryptase to degrade CGRP. We found that CGRP is effectively cleaved by tryptase (Km = 6.8 x 10(-6) mol/L at 37 degrees). Enzymatic activity was inhibited by antipain, leupeptin, N-alpha-p-tosyl-L-lysine chloromethyl ketone, benzamidine or aprotinin, but not by soybean trypsin inhibitor or N-tosyl-L-phenylalanine chloromethyl ketone. The degradation of CGRP by lysates of purified skin mast cells showed a similar pattern of inhibition suggesting that tryptase may be the major enzyme involved. The activity of tryptase was not affected by the presence of heparin. Incubation of CGRP with tryptase resulted in a loss of its vasodilator activity as observed by intravital microscopy of the hamster cheek pouch microvasculature. CGRP preincubated with tryptase failed to relax arterioles when added topically. It is suggested that the catalysis of CGRP by tryptase could represent an important means by which the activity of this neuropeptide is regulated in vivo.

Calcitonin Gene-Related Peptide↗
PubMed1992

Phoneutria nigriventer (armed spider) venom induces increased vascular permeability in rat and rabbit skin in vivo.

The effect of intradermally injected Phoneutria nigriventer venom (PNV) on vascular permeability of both rat and rabbit skin has been investigated. Oedema formation was measured as the local extravascular accumulation at skin sites of intravenously injected 125I-human serum albumin. In both rat and rabbit PNV induced dose-dependent oedema which was greatly potentiated by the vasodilators calcitonin-gene-related peptide and prostaglandin E1. In rats, PNV-induced oedema was markedly reduced either by previous treatment of the animals with the histamine H1 antagonist mepyramine and the serotonin antagonist methysergide or when venom was dialysed, indicating a major role for histamine and serotonin. In rabbits, dialysis of the venom to remove histamine and serotonin did not reduce PNV-induced oedema, indicating presence of oedematogenic component(s) which are different from the amines histamine or serotonin.

Alprostadil↗