The Effects of Antimigraine Drugs on the Vascular Responses by-5-Hydroxytryptamine and Related Biogenic Substances on the External Carotid Bed of Dogs: Possible Pharmacological Implications to Their Antimigraine Action

Saxena, Pramod R.

doi:10.1111/j.1526-4610.1972.hed1202044.x

Cited by 78 publications

(53 citation statements)

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“…Effects of5-hydroxytryptamine in the carotid vascular bed Intracarotid infusions of 5-HT, as we have also found with bolus injections in cervical sympathectomized dogs (Saxena etal., 1971;Saxena, 1972;Saxena & de Vlaam-Schluter, 1974), resulted in a reduction of total carotid blood flow in our pigs. Despite this reduction, tissue blood flow, particularly to the skin and ears (their colour changed to bright red), increased and the AVAs constricted.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, methysergide and the related anti-5-HT drugs, cyproheptadine and mianserin, are not very effective in antagonizing the carotid vasoconstrictor effects of 5-HT (Saxena et al, Correspondence: Professor Pramod R. Saxena. 1971;Saxena, 1972;Spira et al, 1976) indicating that the 5-HT receptors in this vascular region do not resemble the musculotropic 'D' type (Gaddum & Picarelli, 1957) which, in present day terminology, is usually denoted as the 5-HT2 type (Peroutka & Snyder, 1979). Recently, we reported that 5-HT redistributes the carotid blood flow in favour of the nutrient (capillary) fraction, particularly that apportioned to the skin and ears, at the expense of the non-nutrient fraction passing through arterio-venous (A-V) anastomoses (AVAs) (Saxena & Verdouw, 1982).…”

Section: Introductionmentioning

confidence: 99%

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Effects of methysergide and 5‐hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5‐HT receptors

Saxena

Verdouw

1984

British J Pharmacology

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1 The effects of acute (50-350 gg kg-, i.v.) and subacute (350 gg kg-l orally per day for six days) administration of methysergide, and of intra-arterial infusions of 0.5 and 2.0 gkg-min-1 5-hydroxytryptamine (5-HT) on the distribution of carotid blood flow into the capillary (nutrient) and arterio-venous anastomotic (AVA) fractions were studied in anaesthetized pigs. 2 The acute, but not the subacute, administration of methysergide caused a moderate reduction of carotid blood flow. This reduction, noticed only in the AVA fraction, was due to a constriction of the arterio-venous anastomoses (AVAs). 3 Both doses of 5-HT reduced total carotid blood flow but its nutrient fraction -particularly that distributed to the skin and ears -increased substantially. The AVA fraction was greatly diminished. 4 After treatment with methysergide, 5-HT no longer reduced the total carotid blood flow, but increased it. Despite this reversal the constriction of AVAs by the amine was only slightly diminished. On the other hand, the vasodilatation of the nutrient channels was enhanced. 5 The results of the interaction between methysergide and 5-HT provide further evidence for the presence of 'atypical' 5-HT receptors (probably corresponding to 5-HT1 binding sites) mediating AVA contraction and nutrient vasodilatation. The 5-HT2 receptors mediate vasoconstriction and are located in the large conducting arteries and possibly, in smaller numbers, in the AVAs and arterioles.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of methysergide and 5‐hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5‐HT receptors

Saxena

Verdouw

1984

British J Pharmacology

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“…The reason may be that, besides its properties as a 5-HT antag onist, methysergide also acts as a partial agonist on 5-HT receptors, particularly the 5-HTJ receptors (Apperley et aI., 1980;Peroutka, 1984). Moreover, a potentiating effect of methysergide itself on the NE-induced vasoconstriction has been observed in different species (Saxena, 1972;Carroll et ai., 1974;Tsuji and Chiba, 1984;Jandhyala and Kivlighn, 1987), which was also found in the present study.…”

Section: Discussionmentioning

confidence: 99%

Serotonin Potentiates Noradrenaline-Induced Vasoconstriction through 5-HT₁-Type Receptors in Guinea Pig Basilar Artery

Chang

Owman

1989

J Cereb Blood Flow Metab

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Summary: Based on the previous finding that 5-hydroxytryptamine (5-HT) co-exists with norepinephrine (NE) in cerebrovascular sympathetic nerve fibers and can be released during electrical nerve stimulation, the post junctional interaction between the two amines was studied in isolated basilar artery of guinea pig. A low concentration of 5-HT, which in itself has little or no constrictive effect, potentiated the weak contraction of NE by almost 300%. VanNueten et al., 1981VanNueten et al., , 1982 Medgett etal., 1984).Received November 30, 1988; revised April 18, 1989; accepted April 20, 1989. Address correspondence and reprint requests to Prof. C. Owman at Department of Medical Cell Research, Biskopsgatan 5, S-223 62 Lund, Sweden.Abbreviations used: 5-HT, 5-hydroxytryptamine; NE, norepi nephrine. 713by methiothepin, but not by ketanserin, and it could be mimicked by methysergide. The marked potentiation is thus probably associated with the 5-HT I-like receptors, which earlier have been found to mediate the direct va soconstrictive action of 5-HT in this vessel preparation. Key Words: Basilar artery-Guinea pig-5-Hydroxy tryptamine-I-like receptors-5-Hydroxytryptamine po tentiation-Noradrenergic contraction.Usually, the receptors mediating the vasoconstric tive and potentiating effects are of the same subtype and involve mostly the 5-HT2 receptor ( Van Nueten et aI., 1981Medgett et al., 1984;Van Nueten and Janssens, 1986). It has been shown that the post junctional receptors associated with the 5-HT-induced constriction of the basilar artery are 5-HTt-like in the guinea pig, whereas they are of the 5-HT2 type in the rat . METHODSMale guinea pigs weighing 350-500 g were used. They were anesthetized with diethyl ether, and the brain was quickly removed and immersed in a modified Krebs Ringer solution (for composition, see below) at room tem perature. The basilar artery was taken out under a dis section microscope. Ring segments of 1-2 mm in length were cut and mounted between two "L"-shaped stain less-steel holders in 2.5-ml mantled organ baths filled with the Krebs-Ringer solution and aerated by 11.5% CO2 in O2 at 37°C. One holder was connected to a Statham FT03C force-displacement transducer and the other was adjusted to give a resting tension of -1.5-2 mN, which was maintained by repeated adjustments during a 6O-min accommodation period. Isometric tension changes were recorded on a Grass model 7B polygraph.In the studies of the amine interaction in the contractile

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“…These findings have undoubtedly shed light on the mechanisms involved in the carotid vasoconstrictor effects of sumatriptan; nevertheless, the receptor mechanisms involved in the vasoconstrictor effects of 5-HT have not been completely characterized (see for example Saxena, 1972;Mena & Vidrio, 1979;Villalon & Terron 1994a). Hence, this study has investigated the pharmacological profile of the receptors and/or mechanisms involved in the external carotid vasoconstrictor effects of 5-HT in vagosympathectomized dogs; thus, we analysed the effects of the endogenous ligand, 5-HT, in conjunction with those of the 5-HT,-like receptor agonist, sumatriptan (Humphrey et al, 1988;Feniuk et al, 1989).…”

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confidence: 99%

“…Introduction 5-Hydroxytryptamine (5-HT) can produce vasodilatation or vasoconstriction of the canine external carotid bed depending upon the degree of carotid sympathetic tone (Saxena, 1972;Mena & Vidrio, 1979). Hence, we have shown that 5-HT-induced external carotid vasodilatation in dogs with intact sympathetic tone is primarily mediated by an inhibitory action on carotid sympathetic nerves, via the stimulation of prejunctional 5-HTI-like receptors (Villalon et al, 1993a, b;Terron et al, 1994).…”

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Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5‐HT in vagosympathectomized dogs

Villalón

Juan

Castillo³

et al. 1995

British J Pharmacology

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1 5-Hydroxytryptamine (5-HT) can produce vasodilatation or vasoconstriction of the canine external carotid bed depending upon the degree of carotid sympathetic tone. Hence, external carotid vasodilatation to 5-HT in dogs with intact sympathetic tone is primarily mediated by prejunctional 5-HT,-like receptors similar to the 5-HTID subtype, which inhibit the carotid sympathetic outflow. The present investigation is devoted to the pharmacological analysis of the receptors mediating external carotid vasoconstriction by 5-HT in vagosympathectomized dogs. 2 Intracarotid (i.c.) infusions for 1 min of 5-HT (0.3, 1, 3, 10, 30 and 100 Mg) resulted in dosedependent decreases in both external carotid blood flow and the corresponding conductance; both mean arterial blood pressure and heart rate remained unchanged during the infusions of 5-HT. These responses to 5-HT were resistant to blockade by antagonists at 5-HT2 (ritanserin) and 5-HT3/5-HT4 (tropisetron) receptors, but were partly blocked by the 5-HT,-like and 5-HT2 receptor antagonist, methiothepin (0.3 mg kg-1); higher doses of methiothepin (1 and 3 mg kg-') caused little, if any, further blockade. These methiothepin (3 mg kg-')-resistant responses to 5-HT were not significantly antagonized by MDL 72222 (0.3 mg kg-') or tropisetron (3 mg kg-').3 The external carotid vasoconstrictor effects of 5-HT were mimicked by the selective 5-HT,-like receptor agonist, sumatriptan (3, 10, 30 and 100 1g during 1 min, i.c.), which produced dose-dependent decreases in external carotid blood flow and the corresponding conductance; these effects of sumatriptan were dose-dependently antagonized by methiothepin (0.3, 1 and 3 mg kg-'), but not by 5-HTID-like receptor blocking doses of metergoline (0.1 mg kg-'). 4 The above vasoconstrictor effects of 5-HT remained unaltered after administration of phentolamine, propranolol, atropine, hexamethonium, brompheniramine, cimetidine and haloperidol, thus excluding the involvement of a-and f-adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors. Likewise, inhibition of either 5-HT-uptake (with fluoxetine) or cyclo-oxygenase (with indomethacin), depletion of biogenic amines (with reserpine) or blockade of calcium channels (with verapamil) did not modify the effects of 5-HT. 5 Taken together, the above results support our contention that the external carotid vasoconstrictor responses to 5-HT in vagosympathectomized dogs are mainly mediated by activation of sumatriptansensitive 5-HTI-like receptors. It must be emphasized, notwithstanding, that other mechanisms of 5-HT, including an interaction with a novel 5-HT receptor (sub)type and/or an indirect action that may lead to the release of a known (or even unknown) neurotransmitter substance cannot be categorically excluded.

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The Effects of Antimigraine Drugs on the Vascular Responses by-5-Hydroxytryptamine and Related Biogenic Substances on the External Carotid Bed of Dogs: Possible Pharmacological Implications to Their Antimigraine Action

Cited by 78 publications

References 23 publications

Effects of methysergide and 5‐hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5‐HT receptors

Effects of methysergide and 5‐hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5‐HT receptors

Serotonin Potentiates Noradrenaline-Induced Vasoconstriction through 5-HT₁-Type Receptors in Guinea Pig Basilar Artery

Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5‐HT in vagosympathectomized dogs

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The Effects of Antimigraine Drugs on the Vascular Responses by-5-Hydroxytryptamine and Related Biogenic Substances on the External Carotid Bed of Dogs: Possible Pharmacological Implications to Their Antimigraine Action

Cited by 78 publications

References 23 publications

Effects of methysergide and 5‐hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5‐HT receptors

Effects of methysergide and 5‐hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5‐HT receptors

Serotonin Potentiates Noradrenaline-Induced Vasoconstriction through 5-HT1-Type Receptors in Guinea Pig Basilar Artery

Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5‐HT in vagosympathectomized dogs

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Serotonin Potentiates Noradrenaline-Induced Vasoconstriction through 5-HT₁-Type Receptors in Guinea Pig Basilar Artery