Bovine isolated middle cerebral artery contractions to antimigraine drugs

Roon, K. I.; MaassenVanDenBrink, Antoinette; Ferrari, Michel D.; Saxena, Pramod R.

doi:10.1007/s002109900095

Cited by 16 publications

(9 citation statements)

References 28 publications

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“…Similarly, we have previously found that the 5-HT 1B/1D receptor antagonist GR127935, which potently antagonised the sumatriptan-induced constriction of porcine carotid arteriovenous anastomoses (De Vries et al 1998) and bovine isolated middle cerebral artery (Roon et al 1999), failed to affect the ketanserin-resistant constrictor effect of 5-HT. Thus, 5-HT may constrict porcine carotid arteriovenous anastomoses (De Vries et al 1998) and bovine isolated middle cerebral artery (Roon et al 1999) via a novel non-5-HT 1B/1D receptor. It is possible that a part of the constriction of human isolated coronary artery by 5-carboxamidotryptamine in our experiments may be mediated by a GR55562-resistant receptor.…”

Section: Discussionsupporting

confidence: 55%

“…5-Carboxamidotryptamine and 5-HT have a 1000-times higher affinity than sumatriptan (pK i : 8.1, 8.0 and 5.1, respectively) at this recognition site (Castro et al 1997). Similarly, we have previously found that the 5-HT 1B/1D receptor antagonist GR127935, which potently antagonised the sumatriptan-induced constriction of porcine carotid arteriovenous anastomoses (De Vries et al 1998) and bovine isolated middle cerebral artery (Roon et al 1999), failed to affect the ketanserin-resistant constrictor effect of 5-HT. Thus, 5-HT may constrict porcine carotid arteriovenous anastomoses (De Vries et al 1998) and bovine isolated middle cerebral artery (Roon et al 1999) via a novel non-5-HT 1B/1D receptor.…”

Section: Discussionmentioning

confidence: 56%

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Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT_1B/1D Receptor Antagonist GR55562

VanDenBrink

Reekers

Bax

et al. 2000

Pharmacology & Toxicology

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Abstract:The antimigraine drug, sumatriptan, contracts the human coronary artery both in vivo and in vitro. Because sumatriptan has been associated with cardiac side effects, it is important to characterise the receptor involved in sumatriptan-induced coronary artery contraction. Using the agonists sumatriptan and 5-carboxamidotryptamine and the selective 5-HT 1B/1D receptor antagonist GR55562, we have investigated the involvement of 5-HT 1B/1D receptors in the contraction of the human isolated coronary artery. Contractions to sumatriptan (pEC 50 : 6.1∫0.2, maximal effect: 21∫4% of 100 mM K π -induced contraction) were competitively antagonised by GR55562. The pA 2 of GR55562 (7.40∫0.16) was in accord with its reported affinity at the human 5-HT 1B receptor. Since the contractions to 5-carboxamidotryptamine did not reach a maximum with the highest concentration used (10 mM), pEC 50 values could not be calculated for Schild analysis. However, using the pEC 10%Kπ values (negative logarithm of the concentration needed to induce 10% of the contraction to 100 mM K π ), GR55562 proved a less potent antagonist against 5-carboxamidotryptamine than against sumatriptan. These results show that sumatriptan contracts the human isolated coronary artery via 5-HT 1B/1D receptors, most probably the 5-HT 1B subtype. 5-Carboxamidotryptamine may contract the human isolated coronary artery, at least partly, via a novel yet to be characterised, receptor.The human coronary artery contracts in response to the antimigraine drug, sumatriptan, both in vivo (MacIntyre et al. 1993) and in vitro (Connor et al. 1989;Bax et al. 1993;Maassen Van Den Brink et al. 1998). Since sumatriptan has been associated with myocardial infarction (Ottervanger et al. 1993;O'Connor & Gladstone 1995) and cardiac arrest (Kelly 1995) in exceptional cases, it is important to characterise the receptors involved in sumatriptan-induced contraction of the human coronary artery. More knowledge about the receptor mediating coronary artery contraction to sumatriptan may contribute to the development of antimigraine drugs devoid of coronary vasoconstrictor activity.Sumatriptan displays affinity for the 5-HT 1B (pK i : 7.8-8.0), 5-HT 1D (pK i : 8.1-8.5) and the 5-HT 1F (pK i : 7.8-7.9) receptor (Leysen et al. 1996;Razzaque et al. 1999). Human isolated coronary artery contraction to 5-HT is mediated via both 5-HT 1 and 5-HT 2 receptors (Connor et al. 1989;Bax et al. 1993). The contraction mediated by the 5-HT 2 receptor usually exceeds that mediated by 5-HT 1 receptors (Connor et al. 1989;Bax et al. 1993). In some cases, however, 5-HT 1 receptor-mediated contraction is predominant over the 5-HT 2 receptor-mediated contraction (Kaumann et al. 1994). In agreement with the variable contribution of 5-HT 1 receptors in 5-HT-mediated contraction, the contraction to sumatriptan is subject to a high degree of variability Author for correspondence: P. R. Saxena, Department of Pharmacology, Erasmus University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherland...

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 56%

Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT_1B/1D Receptor Antagonist GR55562

VanDenBrink

Reekers

Bax

et al. 2000

Pharmacology & Toxicology

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“…This illustrates that a vasoconstrictor may act on different receptors depending on what part of the vascular tree and species that is examined. Ergotamine and DHE caused constriction of isolated bovine middle cerebral arteries with a pEC50 of 8.0 [28]. Similarly, the pEC50 of ergotamine and DHE for the rat MCA were 7.6-8.7 and 8.4-9.0, respectively, depending on route of administration.…”

Section: Tissue Bath Studiesmentioning

confidence: 87%

Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

2007

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The vasomotor effects of ergotamine and dihydroergotamine (DHE) on the middle cerebral artery (MCA) of rats were studied using the pressurised arteriography method and in vitro myographs. MCAs from Sprague-Dawley rats were mounted on two glass micropipettes using the arteriograph, pressurised to 85 mmHg and luminally perfused. All vessels used attained spontaneous contractile tone (34.9±1.8% of resting tone) and responded to luminal adenosine triphosphate (ATP) with dilatation (24.1±4.0%), which showed functioning endothelium. Luminally added ergotamine or DHE induced maximal contractions of 16.8+8% and 22.4±0.9%, respectively, compared to the resting diameter, with a pEC50 of 8.7±0.1 for ergotamine and 9.0±0.1 for DHE. Abluminal application of ergotamine and DHE also caused concentration-dependent contractions of the perfused MCA by 21.4±2.1% and 23.1±7.0%, respectively, with pEC50 values of 7.6±0.2 for ergotamine and 8.4±0.5 for DHE. The responses were blocked by the 5-HT2A receptor antagonist ketanserin (concentration 10 -12 to 10 -5 M) and partially with the 5-HT1B receptor antagonist BRL-11557PM-B. The 5-HT1D receptor antagonist SB-224289-A had no significant effect. Using a myograph technique, isolated ring segments of the MCA with intact endothelium were mounted on two metal wires. Neither agonist caused relaxation of resting vessels, however, they both responded by weak contractile responses (26±3% of submaximal contractile capacity relative to 60 mM potassium). The contractions were typically slow in on and off set (about 30-60 min). The long duration of ergots should be investigated further in an attempt to design drugs with less recurrence.

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“…Although virtually any blood vessel with an internal diameter as small as 75 µm may be studied, several specific blood vessels have frequently been used to study contractile responses to the triptans. These include bovine cerebral arteries (Roon et al ., 1999; Bouchelet et al ., 2000), which may be obtained from a local slaughterhouse, or the dog or rabbit saphenous vein, as the 5‐HT 1 receptors in these preparations are similar to those in the human cranial or coronary arteries (Gupta et al ., 2004). CGRP receptors have been studied in blood vessels obtained from several species, including pig, guinea pig and rat (Jansen‐Olesen et al ., 2001; Wu et al ., 2002; Gupta et al ., 2004); further studies are awaited to confirm which species provides the best model.…”

Section: Vascular Models For Pharmacological Developmentmentioning

confidence: 99%

Animal models of migraine: looking at the component parts of a complex disorder

Bergerot

Holland

Akerman

et al. 2006

Eur J of Neuroscience

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113

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Animal models of human disease have been extremely helpful both in advancing the understanding of brain disorders and in developing new therapeutic approaches. Models for studying headache mechanisms, particularly those directed at migraine, have been developed and exploited efficiently in the last decade, leading to better understanding of the potential mechanisms of the disorder and of the action for antimigraine treatments. Model systems employed have focused on the pain-producing cranial structures, the large vessels and dura mater, in order to provide reproducible physiological measures that could be subject to pharmacological exploration. A wide range of methods using both in vivo and in vitro approaches are now employed; these range from manipulation of the mouse genome in order to produce animals with human disease-producing mutations, through sensitive immunohistochemical methods to vascular, neurovascular and electrophysiological studies. No one model system in experimental animals can explain all the features of migraine; however, the systems available have begun to offer ways to dissect migraine's component parts to allow a better understanding of the problem and the development of new treatment strategies.

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Bovine isolated middle cerebral artery contractions to antimigraine drugs

Cited by 16 publications

References 28 publications

Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT_1B/1D Receptor Antagonist GR55562

Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT_1B/1D Receptor Antagonist GR55562

Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

Animal models of migraine: looking at the component parts of a complex disorder

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Bovine isolated middle cerebral artery contractions to antimigraine drugs

Cited by 16 publications

References 28 publications

Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT1B/1D Receptor Antagonist GR55562

Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT1B/1D Receptor Antagonist GR55562

Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

Animal models of migraine: looking at the component parts of a complex disorder

Contact Info

Product

Resources

About

Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT_1B/1D Receptor Antagonist GR55562

Human Isolated Coronary Artery Contraction to Sumatriptan Characterised by the Selective 5‐HT_1B/1D Receptor Antagonist GR55562