Effects of Sumatriptan on Capsaicin-Induced Carotid Haemodynamic Changes and CGRP Release in Anaesthetized Pigs

Arulmani, Udayasankar; Heiligers, Jan P.C.; Garrelds, Ingrid M.; Sánchez-López, Araceli; Willems, Edwin; Villalón, Carlos M.; Saxena, Pramod R.

doi:10.1111/j.1468-2982.2004.00743.x

Cited by 13 publications

(14 citation statements)

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“…For this purpose, a 0.5 mm (external diameter) needle, connected to a suitable catheter, was inserted into the right common carotid artery for the continuous infusion of phenylephrine by another motor‐driven syringe. This phenylephrine‐induced carotid vasoconstriction, which allowed us to obtain greater vasodilator responses (Arulmani et al ., 2004a), was compared with the effects produced after 10‐min i.v. infusions of the highest doses of sumatriptan, donitriptan, PNU‐142633, PNU‐109291 or equivalent volumes of physiological saline.…”

Section: Methodssupporting

confidence: 88%

“…The release of endogenous CGRP can be experimentally induced by either trigeminal electrical stimulation (Buzzi et al ., 1991; Goadsby and Edvinsson, 1993) or chemical stimulation with capsaicin (Potenza et al ., 1994; Hou et al ., 2002; Dux et al ., 2003). Interestingly, the water‐soluble antimigraine drug, sumatriptan (see Humphrey et al ., 1991), attenuated the increased release of CGRP evoked by trigeminal electrical stimulation in rats and cats (Buzzi et al ., 1991; Goadsby and Edvinsson, 1993), but failed to modify the carotid vasodilatation and the increased release of CGRP induced by capsaicin in pigs (Arulmani et al ., 2004a). In this context, it is noteworthy that sumatriptan does not easily cross an intact blood–brain barrier (see Humphrey et al ., 1991).…”

Section: Introductionmentioning

confidence: 99%

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Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT_1B rather than 5‐HT_1D receptors

Muñoz-Islas¹,

Gupta

Jiménez-Mena³

et al. 2006

British J Pharmacology

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Background and purpose: It has been suggested that during a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the effects of the agonists sumatriptan (5-HT 1B/1D water-soluble), donitriptan (5-HT 1B/1D lipid-soluble), PNU-142633 (5-HT 1D water-soluble) and PNU-109291 (5-HT 1D lipid-soluble) on vasodilator responses to capsaicin, a-CGRP and acetylcholine in dog external carotid artery. Experimental approach: 59 vagosympathectomized dogs were anaesthetized with sodium pentobarbitone. Blood pressure and heart rate were recorded with a pressure transducer, connected to a cannula inserted into a femoral artery. A precalibrated flow probe was placed around the common carotid artery, with ligation of the internal carotid and occipital branches, and connected to an ultrasonic flowmeter. The thyroid artery was cannulated for infusion of agonists. Key results: Intracarotid infusions of capsaicin, a-CGRP and acetylcholine dose-dependently increased blood flow through the carotid artery. These responses remained unaffected after intravenous (i.v.) infusions of sumatriptan, PNU-142633, PNU-109291 or physiological saline; in contrast, donitriptan significantly attenuated the vasodilator responses to capsaicin, but not those to a-CGRP or acetylcholine. Only sumatriptan and donitriptan dose-dependently decreased the carotid blood flow. Interestingly, i.v. administration of the antagonist, SB224289 (5-HT 1B ), but not of BRL15572 (5-HT 1D ), abolished the inhibition by donitriptan. Conclusions and implications: Our results suggest that the inhibition produced by donitriptan of capsaicin-induced external carotid vasodilatation is mainly mediated by 5-HT 1B , rather than 5-HT 1D , receptors, probably by a central mechanism.

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Section: Methodssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT_1B rather than 5‐HT_1D receptors

Muñoz-Islas¹,

Gupta

Jiménez-Mena³

et al. 2006

British J Pharmacology

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“…Summ et al 24 found that a TRPV1 antagonist did not affect responding to mechanically induced cortical spreading depression or to electrical stimulation of the middle meningeal artery/dura mater, although it did affect response to capsaicin stimulation. Arulmani et al 25 found that sumatriptan did not inhibit CGRP release from intracarotid capsaicin injections and concluded that sumatriptan's main effect must then be to promote cranial vasoconstriction. Yan et al 26 found that acid‐sensitive currents in dural neurons were not modulated by capsazepine, a TRPV1 antagonist, but were strongly affected by amiloride, an acid‐sensing ion channel antagonist.…”

Section: Discussionmentioning

confidence: 99%

Sumatriptan Inhibits TRPV1 Channels in Trigeminal Neurons

et al. 2012

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Objective To understand a possible role for transient potential receptor vanilloid 1 (TRPV1) ion channels in sumatriptan relief of pain mediated by trigeminal nociceptors. Background TRPV1 channels are expressed in small nociceptive sensory neurons. In dorsal root ganglia (DRG), TRPV1-containing nociceptors mediate certain types of inflammatory pain. Neurogenic inflammation of cerebral dura and blood vessels in the trigeminal nociceptive system is thought to be important in migraine pain, but the ion channels important in transducing migraine pain are not known. Sumatriptan is an agent effective in treatment of migraine and cluster headache. We hypothesized that sumatriptan might modulate activity of TRPV1 channels found in the trigeminal nociceptive system. Methods We used immunohistochemistry to detect the presence of TRPV1 channel protein, whole cell recording in acutely dissociated trigeminal ganglia (TG) to detect functionality of TRPV1 channels, and whole cell recording in trigeminal nucleus caudalis (TNC) to detect effects on release of neurotransmitters from trigeminal neurons onto second order sensory neurons. Effects specifically on TG neurons that project to cerebral dura were assessed by labeling dural nociceptors with DiI. Results Immunohistochemistry demonstrated that TRPV1 channels are present in cerebral dura, trigeminal ganglion, and in the trigeminal nucleus caudalis. Capsaicin, a TRPV1 agonist, produced depolarization and repetitive action potential firing in current clamp recordings and large inward currents in voltage clamp recordings from acutely dissociated TG neurons, demonstrating that TRPV1 channels are functional in trigeminal neurons. Capsaicin increased spontaneous excitatory postsynaptic currents (sEPSCs) in neurons of layer II in TNC slices, showing that these channels have a physiological effect on central synaptic transmission. Sumatriptan (10 μM), a selective anti-migraine drug inhibited TRPV1-mediated inward currents in TG. and capsaicin-elicited sEPSCs in TNC slices. The same effects of capsaicin and sumatriptan were found in acutely dissociated DiI-labeled TG neurons innervating cerebral dura. Conclusion Our results build on previous work indicating that TRPV1 channels in trigeminal nociceptors play a role in craniofacial pain. Our findings that TRPV1 is inhibited by the specific antimigraine drug sumatriptan, and that TRPV1 channels are functional in neurons projecting to cerebral dura suggests a specific role for these channels in migraine or cluster headache.

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“…Involvement of CGRP in the pathophysiology of migraine is further strengthened by the observation that olcegepant (BIBN4096BS, Doods et al 2000), a CGRP receptor antagonist, is effective in the acute treatment of migraine attacks (Olesen et al 2004). Capsaicin has been widely used in various in vivo models of migraine to induce cranial vasodilatation, which is attributed to endogenous release of neuropeptides, especially CGRP (Akerman et al 2003; Arulmani et al 2004a; Gupta et al 2006a). The involvement of CGRP is further substantiated in all these in vivo studies by the fact that the capsaicin-induced vascular responses are all amenable to blockade with CGRP receptor antagonists.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries

Gupta

Lozano-Cuenca

Villalón

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Capsaicin, a pungent constituent from red chilli peppers, activates sensory nerve fibres via transient receptor potential vanilloid receptors type 1 (TRPV1) to release neuropeptides like calcitonin gene-related peptide (CGRP) and substance P. Capsaicin-sensitive nerves are widely distributed in human and porcine vasculature. In this study, we examined the mechanism of capsaicin-induced relaxations, with special emphasis on the role of CGRP, using various pharmacological tools. Segments of human and porcine proximal and distal coronary arteries, as well as cranial arteries, were mounted in organ baths. Concentration response curves to capsaicin were constructed in the absence or presence of the CGRP receptor antagonist olcegepant (BIBN4096BS, 1 μM), the neurokinin NK 1 receptor antagonist L-733060 (0.5 μM), the voltagesensitive calcium channel blocker ruthenium red (100 μM), the TRPV1 receptor antagonist capsazepine (5 μM), the nitric oxide synthetase inhibitor N ω -nitro-Larginine methyl ester HCl (L-NAME; 100 μM), the gap junction blocker 18α-glycyrrhetinic acid (10 μM), as well as the RhoA kinase inhibitor Y-27632 (1 μM). Further, we also used the K + channel inhibitors 4-aminopyridine (1 mM), charybdotoxin (0.5 μM)+apamin (0.1 μM) and iberiotoxin (0.5 μM)+apamin (0.1 μM). The role of the endothelium was assessed by endothelial denudation in distal coronary artery segments. In distal coronary artery segments, we also measured levels of cyclic adenosine monophosphate (cAMP) after exposure to capsaicin, and in human segments, we also assessed the amount of CGRP released in the organ bath fluid after exposure to capsaicin. Capsaicin evoked concentration-dependent relaxant responses in precontracted arteries, but none of the abovementioned inhibitors did affect these relaxations. There was no increase in the cAMP levels after exposure to capsaicin, unlike after (exogenously administered) α-CGRP. Interestingly, there were significant increases in CGRP levels after exposure to vehicle (ethanol) as well as capsaicin, although this did not induce relaxant responses. In conclusion, the capsaicin-induced relaxations of the human and porcine distal coronary arteries are not mediated by CGRP, NK 1 , NO, vanilloid receptors, voltage-sensitive calcium channels, K + channels or cAMP-mediated mechanisms. Therefore, these relaxant responses to capsaicin are likely to be attributed to a non-specific, CGRP-independent mechanism.

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Effects of Sumatriptan on Capsaicin-Induced Carotid Haemodynamic Changes and CGRP Release in Anaesthetized Pigs

Cited by 13 publications

References 50 publications

Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT_1B rather than 5‐HT_1D receptors

Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT_1B rather than 5‐HT_1D receptors

Sumatriptan Inhibits TRPV1 Channels in Trigeminal Neurons

Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries

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Effects of Sumatriptan on Capsaicin-Induced Carotid Haemodynamic Changes and CGRP Release in Anaesthetized Pigs

Cited by 13 publications

References 50 publications

Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT1B rather than 5‐HT1D receptors

Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT1B rather than 5‐HT1D receptors

Sumatriptan Inhibits TRPV1 Channels in Trigeminal Neurons

Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries

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Product

Resources

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Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT_1B rather than 5‐HT_1D receptors

Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT_1B rather than 5‐HT_1D receptors