Serotonin Antagonism in Isolated Canine Cerebral Arteries

Toda, Noboru; Hayashi, Shigehiro; Fu, Wang L.H.; Nagasaka, Yasunori

doi:10.1254/jjp.26.57

Cited by 24 publications

(5 citation statements)

References 20 publications

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“…The combination of increasing concentrations of ergotamine with 5-HT produced a series of dose-response curves starting from progressively higher baselines and with dosedependently diminished maxima. Similar curves were observed by TODA et al [16] when the 5-HT antagonism of ergotamine was investigated on canine cerebral arteries. Since in arterial vascular smooth muscle the intrinsic activity of ergotamine is suggested to be mediated through stimulation of 5-HT receptors [9,10], ergotamine may thus be regarded as a non-competitive dualist acting at 5-HT receptors.…”

Section: ]supporting

confidence: 85%

Regional differences in the responsiveness of isolated arteries from cattle, dog and man

Müller‐Schweinitzer¹,

Weidmann²

1977

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Changes in tension of spiral strips from basilar, external carotid, temporal and muscle arteries from cattle, dog and man were monitored isometrically. Dose-response curves for 5-HT, noradrenaline and ergotamine indicated a variation in responsiveness between different arteries of the same species as well as between the same arteries of different species. When tested against 5-HT ergotamine consistently acted as non-competitive dualist but it antagonized responses to to noradrenaline only in peripheral arteries from dog and man. In all arteries from the carotid vasculature and in bovine muscle arteries the vasoconstrictor effects of ergotamine and noradrenaline were independent additive. It is suggested that the therapeutic value of ergotamine in the treatment of migraine headache is due to its selective vasoconstrictor activity in the external carotid vasculature mediated through independent additive vasoconstrictor effects of ergotamine and noradrenaline.

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Section: ]supporting

confidence: 85%

Regional differences in the responsiveness of isolated arteries from cattle, dog and man

Müller‐Schweinitzer¹,

Weidmann²

1977

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“…Central serotonergic systems arising in the mesencephalic raphé nuclei are known to be involved in the modulation of diverse brain functions, including appetite control, sleep, memory and learning, temperature regulation, mood and endocrine regulation. In addition to these neuromodulatory roles, there is also evidence that cerebral blood vessels are innervated from within the brain by serotonergic neurons (Steinbusch, 1981; Edvinsson et al ., 1985; Scatton et al ., 1985; Bonvento et al ., 1991) and a number of studies have shown 5‐HT to be a potent cerebrovascular constrictor, both in vitro (Forster et al ., 1983; Toda et al ., 1976; Fu & Toda, 1983) and in situ (Edvinsson et al ., 1976). Although these studies examined large cerebral arteries and pial arterioles following circumvention of the blood brain barrier, 5‐HT administered systemically produces reductions in cerebral blood flow in the whole animal (Harper & MacKenzie, 1977; Grome & Harper, 1983) and pharmacological inhibition of endogenous 5‐HT release, by systemic application of an agonist specific for the 5‐HT 1A autoreceptor, was found to induce increases in LCBF in the otherwise physiologically normal rat (McBean et al ., 1991).…”

Section: Discussionmentioning

confidence: 99%

Persistent cerebrovascular effects of MDMA and acute responses to the drug

Ferrington

Kirilly²,

McBean

et al. 2006

Eur J of Neuroscience

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Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287-295]. In the longer term the same single dose results in depletion of 5-hydroxytrptamine (5-HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre-treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre-treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [(14)C]-iodoantipyrine and [(14)C]-2-deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [(3)H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment there were significant reductions in densities of 5-HT transporter (SERT)-positive fibres (-46%) and [(3)H]-paroxetine binding (-47%). In animals pre-treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre-treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA-pre-treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA-induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5-HT terminals. However, there may be a sub-population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.

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“…This is compatible with effects of 5-HT on isolated vascular smooth muscle preparations from various animal species (e.g. 11,13,22,23,24,25,26,27). In these animal studies the experimental design included consecutive 5-HT stimulations, for which reason tachyphylaxis to this agent must have been excluded.…”

Section: Discussionmentioning

confidence: 78%

Effects of 5-Hydroxytryptamine and Ergotamine on Human Superficial Temporal Artery

1981

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Isometric tension was recorded in ring preparations of human superficial temporal arteries contracted by noradrenaline (NA), 5-hydroxytryptamine (5-HT), and ergotamine. In contrast to NA and 5-HT, ergotamine induced long-lasting contractions refractive to additional stimulations and resistant to repeated wash-out. When tested against 5-HT, ergotamine acted as a non-competitive antagonist. When repeating the 5-HT stimulations (4.7 x 10(-5) M) the contractile response decreased indicating tachyphylaxis to this agent. As ergotamine revealed both a vasoconstrictive and a 5-HT-blocking activity, the beneficial effect in migraine may be by an interference during both the vasoconstrictory and vasodilatory phases.

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Serotonin Antagonism in Isolated Canine Cerebral Arteries

Abstract: Abstract-In

Cited by 24 publications

References 20 publications

Regional differences in the responsiveness of isolated arteries from cattle, dog and man

Regional differences in the responsiveness of isolated arteries from cattle, dog and man

Persistent cerebrovascular effects of MDMA and acute responses to the drug

Effects of 5-Hydroxytryptamine and Ergotamine on Human Superficial Temporal Artery

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