Advertisement

Presence of 5-hydroxytryptamine in adrenergic nerves of the brain circulation: its role in sympathetic neurotransmission and regulation of the cerebral vessel wall

  • Christer Owman
  • Jing-Yu Chang
  • Jan Erik Hardebo
Chapter
Part of the Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine book series (DICM, volume 106)

Abstract

It has for long been believed that 5-hydroxytryptamine (5-HT) plays an aetiological role in some important cerebral vascular disorders, such as migraine and vasospasm following subarachnoid hemorrhage [1–6]. This is related to the strong vasoconstrictor action of 5-HT on brain vessels in vitro [7, 8]. When infused into the carotid artery, it reduces cerebral blood flow in many brain regions, provided the blood-brain barrier is opened or monoamine oxidase is inhibited. The response seems to be partly associated with a decrease in cerebral metabolism [9–11].

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Deshmukh VD, Harper AM (1973): The effect of serotonin on cerebral and extracerebral blood flow with possible implications in migraine. Acta Neurol Scand 49: 649–658.PubMedCrossRefGoogle Scholar
  2. 2.
    Allen GS, Henderson LM, Chou SN, French LA (1974): Cerebral arterial spasm. Part 2: In vitrocontractile activity of serotonin in human serum and CSF on the canine basilar artery, and its blockage by methysergide and phenoxybenzamine. J Neurosurg 40: 442–450.PubMedCrossRefGoogle Scholar
  3. 3.
    Sjaastad O (1975): The significance of blood serotonin levels in migraine. Acta Neurol Scand 51: 200–210.PubMedCrossRefGoogle Scholar
  4. 4.
    Owman Ch, Edvinsson L, Olin T, Sahlin Ch, Svendgaard N-Aa (1979): Pathophysiology of cerebral vasospasm: Transmitter changes in perivascular sympathetic nerves, and increased pial artery sensitivity to norepinephrine and serotonin, pp. 295–305 in: Price T R, Nelson E (eds), Cerebrovascular Disease. New York: Raven Press.Google Scholar
  5. 5.
    Pickard JD, Perry S (1984): Spectrum of altered reactivity of isolated cerebral arteries following subarachnoid haemorrhage—response to potassium, pH, noradrenaline, 5-hydroxytryptamine, and sodium loading. J Cereb Blood Flow Metab 4: 599–609.PubMedCrossRefGoogle Scholar
  6. 6.
    Fozard JR (1985): 5-Hydroxytryptamine in the pathophysiology of migraine, pp. 321–328 in: Bevan JA, Godfraind T, Maxwell RA, Stoclet JC, Worcel, W (eds), Vascular Neuroeffector Mechanisms. Amsterdam: Elsevier.Google Scholar
  7. 7.
    Edvinsson L, Hardebo JE, Owman Ch (1978): Pharmacological analysis of 5-hydroxy-tryptamine receptors in isolated intracranial and extracranial vessels of cat and man. Circ Res 42: 143–151.PubMedCrossRefGoogle Scholar
  8. 8.
    Hardebo JE, Edvinsson L, Owman Ch, Svendgaard N-Aa (1978): Potentiation and antagonism of serotonin effects on intracranial and extracranial vessels. Neurology 28: 64–70.PubMedCrossRefGoogle Scholar
  9. 9.
    Harper AM, MacKenzie ET (1977): Cerebral circulatory and metabolic effects of 5-hydroxytryptamine in anaesthetised baboons.J Physiol 271: 721–733.Google Scholar
  10. 10.
    Eidelman BN, Mendelow AD, McCalden TA, Bloom DS (1978): Potentiation of cerebrovascular response to intra-arterial 5-hydroxytryptamine. Am J Physiol 234: H300– H304.PubMedGoogle Scholar
  11. 11.
    Grom JJ, Harper AM (1983): The effects of serotonin on local cerebral blood flow. J Cereb Blood Flow Metab 3: 71–77.CrossRefGoogle Scholar
  12. 12.
    Chan-Palay V (1976): Serotonin axons in the supra- and subependymal plexuses and in the leptomeninges: their roles in local alterations of cerebrospinal fluid and vasomotor activity. Brain Res 102: 103–130.PubMedCrossRefGoogle Scholar
  13. 13.
    Steinbusch HWM, Verhofstad AAJ, Joosten HWJ (1978): Localization of serotonin in the central nervous system by immunohistochemistry: Description of a specific and sensitive technique and some applications. Neuroscience 3: 811–819.PubMedCrossRefGoogle Scholar
  14. 14.
    Griffith SG, Lincoln J, Burnstock G (1982): Serotonin as a neurotransmitter in cerebral arteries. Brain Res 247: 388–392.PubMedCrossRefGoogle Scholar
  15. 15.
    Griffith SG, Burnstock G (1983): Immunohistochemical demonstration of serotonin in nerves supplying human cerebral and mesenteric blood vessels. Lancet 1: 561–562.PubMedCrossRefGoogle Scholar
  16. 16.
    Edvinsson L, Degueurce A, Duverger D, MacKenzie ET, Scatton B (1983): Central serotonergic nerves project to the pial vessels of the brain. Nature 306: 55–57.PubMedCrossRefGoogle Scholar
  17. 17.
    Edvinsson L, Birath E, Uddman R, Lee TJF, Duverger D,Mackenzie ET, Scatton B (1984): Indoleaminergic mechanisms in brain vessels: Localization, concentration, uptake and in vitro responses of 5–hydroxytryptamine. Acta Physiol Scand 121: 291–299.Google Scholar
  18. 18.
    Alafaci C, Cowen T, Crockard HA, Burnstock G (1986): Cerebral perivascular serotonergic fibres have a peripheral origin in the gerbil. Brain Res Bull 16: 303–304.PubMedCrossRefGoogle Scholar
  19. 19.
    Cowen T, Alafaci C, Crockard HA, Burnstock G (1986): 5-HT-containing nerves to major cerebral arteries of gerbil originate in the superior cervical ganglia. Brain Res 384: 51–59.PubMedCrossRefGoogle Scholar
  20. 20.
    Cowen T, Alafaci C, Crockard HA, Burnstock G (1987): Origin and postnatal development of nerves showing 5-hydroxytryptamine-like immunoreactivity supplying major cerebral arteries of the rat. Neurosci Lett 78: 121–126.PubMedCrossRefGoogle Scholar
  21. 21.
    Chang J–Y, Owman Ch (1986): Immunohistochemical and pharmacological studies on serotonergic nerves and receptors in brain vessels. Acta Physiol Scand 127 suppl. 552: 49–53.Google Scholar
  22. 22.
    Chang J–Y, Hardebo JE, Owman Ch, Sahlin Ch, Svendgaard N-Aa (1987): Nerves containing serotonin, its interaction with noradrenaline and characterization of serotonergic receptors in cerebral arteries of monkey. J Auton Pharmacol 7: 317–329.PubMedCrossRefGoogle Scholar
  23. 23.
    Reinhard JF, Liebmann JE, Schlosberg AJ, Moskowitz MA (1979): Serotonin neurons project to small blood vessels in the brain. Science 206: 85–87.PubMedCrossRefGoogle Scholar
  24. 24.
    Marco EJ, Belfagon G, Salaices M, Sanchez-Ferrer C, Marin J (1985): Serotonergic innervation of cat cerebral arteries. Brain Res 338: 137–139.PubMedCrossRefGoogle Scholar
  25. 25.
    Scatton B, Duverger D, L’Hereux R, Serrano A, Fage D, Nowicki JP, MacKenzie ET (1985): Neurochemical studies on the existence, origin and characteristics of the serotonergic innervation of small pial vessels. Brain Res 345: 219–229.PubMedCrossRefGoogle Scholar
  26. 26.
    Levitt B, Duckies SP (1986): Evidence against serotonin as a vasoconstrictor neurotransmitter in the rabbit basilar artery.J Pharmacol Exp Ther 238: 880–885.Google Scholar
  27. 27.
    Amenta F, De Rossi M, Mione MC, Geppetti P (1985): Characterization of 3H-5-hydrox-ytryptamine uptake within rat cerebrovascular tree. Eur J Pharmacol 112: 181–186.PubMedCrossRefGoogle Scholar
  28. 28.
    Tsai SH, Lin SZ, Wang SD, Liu JC, Shih CJ (1985): Retrograde localization of the innervation of the middle cerebral artery with horseradish peroxidase in cats. Neurosurgery 16: 463–467.PubMedCrossRefGoogle Scholar
  29. 29.
    Saito A, Lee TJ–F (1987): Serotonin as an alternative transmitter in sympathetic nerves of large cerebral arteries of the rabbit. Circ Res 60: 220–228.PubMedCrossRefGoogle Scholar
  30. 30.
    Verhofstad AAJ, Steinbusch HWM, Penke B, Varga J, Joosten HWJ (1981): Serotonin- immunoreactive cells in superior cervical ganglion of the rat: Evidence for the existence of separate serotonin and catecholamine containing small ganglionic cells. Brain Res 212: 39–49.PubMedCrossRefGoogle Scholar
  31. 31.
    Häppölä O, Päivärinta H, Soinila S, Steinbusch HWM (1986): Pre- and postnatal development of 5-hydroxytryptamine-immunoreactive cells in the superior cervical ganglion of the rat. J Auton Nerv Syst 15: 21–31.PubMedCrossRefGoogle Scholar
  32. 32.
    Häppölä O, Soinila S, Lahtinen T, Joh TH, Steinbusch HWM (1987): Immunohistochemical localization of 5-hydroxytryptamine in principal neurons and nerve fibers of the rat superior cervical ganglion. Neuroscience 22 (suppl.): S813.Google Scholar
  33. 33.
    Sah DWY, Matsumoto SG (1987): Evidence for serotonin synthesis, uptake and release in dissociated rat sympathetic neurons in culture. JNeurosci 7: 391–399.Google Scholar
  34. 34.
    Owman Ch (1964): Sympathetic nerves probably storing two types of monoamines in the rat pineal gland. Int J Neuropharmacol 2: 105–11CrossRefGoogle Scholar
  35. 35.
    Thoa NB, Eccleston D, Axelrod J (1969): The accumulation of C14 serotonin in the guinea-pig vas deferens.J Pharmacol Exp Ther 169: 68–73.Google Scholar
  36. 36.
    Kawasaki H, Takasaki K (1984): Vasoconstrictor response induced by 5-hydroxytryptamine released from vascular adrenergic nerves by periarterial nerve stimulation. J Pharmacol Exp Ther 229: 816–822.PubMedGoogle Scholar
  37. 37.
    Cohen RA (1984): Platelet-induced neurogenic coronary contractions due to accumulation of the false neurotransmitter, 5-hydroxytryptamine. J Clin Invest 75: 286–292.CrossRefGoogle Scholar
  38. 38.
    Paiva MQ, Caramona M, Osswald W (1984): Intra- and extraneuronal metabolism of 5–hydroxytryptamine in the isolated saphenous vein of the dog. Naunyn-Schmiedeberg’s Arch Pharmacol 325: 62–68.CrossRefGoogle Scholar
  39. 39.
    Verbeuren TJ, Jordaens EH, Herman AG (1983): Accumulation and release of 3H-5-hydroxytryptamine in saphenous veins and cerebral arteries of dog. J Pharmacol Exp Ther 226: 579–588.PubMedGoogle Scholar
  40. 40.
    Ross SB (1982): The characteristics of serotonin uptake systems, pp. 159–195 in: Osborne NN (ed), Biology of Serotonergic Transmission. John Wiley & Sons Ltd: Chichester, New York, Brisbane, Toronto.Google Scholar
  41. 41.
    Jandhyala BS, Kivlighn SD (1987): Antagonism by methysergide of neurogenic vasoconstriction in the dog forelimb. Fed Proc 46: 276–280.PubMedGoogle Scholar
  42. 42.
    Chang J-Y, Owman Ch, Steinbusch HWM (1988): Evidence for coexistence of serotonin and noradrenaline in sympathetic nerves supplying brain vessels of guinea-pig. Brain Res 438: 237–246.PubMedCrossRefGoogle Scholar
  43. 43.
    Chang J-Y, Ekblad E, Kannisto P, Owman Ch (1989): Serotonin uptake into cerebrovascular nerve fibers of rat, visualization by immunohistochemistry, disappearance following sympathectomy, and release during electrical stimulation. Brain Res 492: 79–88.PubMedCrossRefGoogle Scholar
  44. 44.
    Kajikawa H (1968): Flourescence histochemical studies on the distribution of adrenergic nerve fibers to intracranial blood vessels. Arch Jap Chir 37: 473–484.Google Scholar
  45. 45.
    Kajikawa H (1969): Mode of the sympathetic innervation of the cerebral vessels demonstrated by the fluorescent histochemical technique in rat and cat. Arch Jap Chir 38: 227–235.Google Scholar
  46. 46.
    Arbab MAR, Delgado TJ, Wiklund L, Svendgaard N-Aa (1989): Stellate ganglion innervation of the vertebra-basilar arterial system demonstrated in the rat with anterograde and retrograde WGA–HRP tracing. Brain Res 445: 175–180.CrossRefGoogle Scholar
  47. 47.
    Chang J-Y, Hardebo JE, Owman Ch (1989): Kinetic studies on uptake of serotonin and noradrenaline into pial arteries of rats. J Cereb Blood Flow Metab in press.Google Scholar
  48. 48.
    Owman Ch, Chang J-Y, Ekblad E, Steinbusch HWM (1987): Immunohistochemical investigation of the relationship between different neuropeptides and amine transmitters in monkey and guinea-pig cerebral arteries, pp. 355–370 in: Nobin A, Owman Ch, Arneklo-Nobin B (eds), Neuronal Messengers in Vascular Function. Elsevier: New York, Oxford, Amsterdam.Google Scholar
  49. 49.
    Breese GR, Traylor TD (1970): Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: Evidence for selective degeneration of catecholamine neurons. J Pharmacol Exp Ther 174: 413–420.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Baumgarten HG, Evetts KD, Holman RB, Iversen LL, Vogt M, Wilson G (1972): Effect of 5,6-hydroxytryptamine on monoaminergic neurones in the central nervous system of the rat. /Neurochem 19: 1587–1597.Google Scholar
  51. 51.
    Björklund A, Horn AS, Baumgarten HG, Nobin A, Schlossberger HG (1975): Neurotoxicity of hydroxylated tryptamines: Structure-activity relationships. 2. In vitro studies on monoamine uptake inhibition and uptake impairments. Acta Physiol Scand(suppl.) 429: 31–60.Google Scholar
  52. 52.
    Shaskan EG, Snyder SH (1970): Kinetics of serotonin accumulation into slices from rat brain: Relationship to catecholamine uptake. J Pharmacol Exp Ther 175: 404–418.PubMedGoogle Scholar
  53. 53.
    Kuhar MJ, Roth RH, Aghajanian G (1972): Synaptosomes from forebrains of rats with midbrain raphe lesions: Selective reduction of serotonin uptake. J Pharmacol Exp Ther 181: 36–45.PubMedGoogle Scholar
  54. 54.
    Lundberg JM, Terenius L, Hökfelt T, Martling CR, Tatemoto K, Mutt V, Polak J, Bloom S, Goldstein M (1982): Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand 116: 477–480.PubMedCrossRefGoogle Scholar
  55. 55.
    Lundberg JM, Saria A, Hökfelt T, Franco-Cereceda A, Terenius L (1985): Tissue-specific depletion of NPY-like immunoreactivity by reserpine. Acta Physiol Scand 123: 363–365.PubMedCrossRefGoogle Scholar
  56. 56.
    Stjernquist M, Owman Ch (1987): Interaction of noradrenaline, NPY and VIP with the neurogenic cholinergic response of the rat uterine cervix in vitro. Acta Physiol Scand 131: 553–562.PubMedCrossRefGoogle Scholar
  57. 57.
    Lightman SL, Iversen LL (1969): The role of uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart. Br J Pharmacol 37: 638–649.PubMedCrossRefGoogle Scholar
  58. 58.
    Ross SB, Renyi AL (1969): Inhibition of the uptake of tritiated 5-hydroxytryptamine in brain tissue. Eur J Pharmacol 7: 270–277.PubMedCrossRefGoogle Scholar
  59. 59.
    Ross SB, Renyi AL (1975): Tricylic antidepressant agents. I. Comparison of the inhibition of the uptake of 3H-noradrenaline and 14C-5-hydroxytryptamine into crude synaptosome preparations of the midbrain-hypothalamus region of the rat brain. Acta Pharmacol Toxicol 36: 382–394.CrossRefGoogle Scholar
  60. 60.
    Gershon MD, Altman KF, (1971): Analysis of the uptake of 5-hydroxytryptamine by the myenteric plexus of small intestine of the guinea-pig. J Pharmacol Exp Ther 179: 29–41.PubMedGoogle Scholar
  61. 61.
    Alm P, Owman Ch, Sjöberg N-O, Thorbert G (1979): Uptake and metabolism of 3H-norepinephrine in uterine nerves of pregnant guinea–pig. Am J Physiol 236: C277–C285.Google Scholar
  62. 62.
    Koevary SB, Azmitia EC, McEvoy RC (1983): Rat pancreatic serotonergic nerves: Morphologic, pharmacological and physiological studies. Brain Res 265: 328–332.PubMedCrossRefGoogle Scholar
  63. 63.
    Fuxe K, Ungerstedt U (1968): Histochemical studies on the distribution of catecholamines and 5-hydroxytryptamine after intraventricular injection. Histochemie 13: 16–28.PubMedCrossRefGoogle Scholar
  64. 64.
    Iversen LL (1970): Neuronal uptake processes for amines and amino acids, pp. 109–132 in: Costa E, Giacobini E (eds), Advances in Biochemical Psychopharmacology. Vol. 2. New York: Raven Press.Google Scholar
  65. 65.
    Magnussen I, Tønner K, Engbaek F (1982): Paroxetine, a potent selective long-acting inhibitor of synaptosomal 5-HT uptake in mice. J Neural Transm 55: 217–226.CrossRefGoogle Scholar
  66. 65a.
    Engbaek F and Voldby B (1982): Radioimmunoassay of serotonin (5-hydroxytryptamine) in cerebrospinal fluid, plasma and serum. Clin Chem 28: 624–628.PubMedGoogle Scholar
  67. 66.
    Crawford N (1965): Systemic venous platelet-bound and plasma free serotonin levels in non–carcinoid malingancy. Clin Chem Acta 12: 274–281.CrossRefGoogle Scholar
  68. 67.
    Genefke IK, Garel A, Mandel P (1968): Factors influencing free serotonin in human plasma. Clin Chem Acta 20: 61–67.CrossRefGoogle Scholar
  69. 68.
    Hardebo JE, Owman Ch (1980): Barrier mechanisms for neurotransmitter monoamines and their precursor at the blood-brain interface. Ann Neurol 8: 1–11.PubMedCrossRefGoogle Scholar
  70. 69.
    Maruki C, Spatz M, Ueki Y, Nagatsu I, Bembry J (1984): Cerebrovascular endothelial cell culture: Metabolism and synthesis of 5-hydroxytryptamine. J Neurochem 43: 316–319.PubMedCrossRefGoogle Scholar
  71. 70.
    Edvinsson L, Cervós-Navarro J, Larsson L-I, Owman Ch, Ronnberg A-L (1977): Regional distribution of mast cells containing histamine, dopamine, or 5-hydroxytrypta- mine in mammalian brain. Neurology 27: 878–883.PubMedCrossRefGoogle Scholar
  72. 71.
    Dimitriadou V, Aubineau P, Taxi J, Seylaz J (1987): Ultrastructural evidence for a functional unit between nerve fibers and type II cerebral mast cells in the cerebral vascular wall. Neuroscience 22: 621–630.PubMedCrossRefGoogle Scholar
  73. 72.
    Green JP, (1966): Synthesis, uptake and binding of histamine and 5-hydroxytrytamine in mast cells, pp. 125–145 in: Euler US von, Rosell S, Uvnäs B (eds), Mechanisms of Release of Biogenic Amines. Oxford: Pergamon Press.Google Scholar
  74. 73.
    Chang J-Y, Owman Ch (1989): Cerebrovascular serotonergic receptors mediating vasoconstriction: Further evidence for the existence of 5-HT2 receptors in rat and 5-HT1 like receptors in guinea-pig basilar arteries. Acta Physiol Scand 136: 59–67.PubMedCrossRefGoogle Scholar
  75. 74.
    Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982): 3H Ketanserin (R41 468) a selective 3H ligand for serotonin2 receptor binding sites. Mol Pharmacol 21: 301–314.PubMedGoogle Scholar
  76. 75.
    Feniuk W, Humphrey PPA, Perren MJ, Watts AD (1985): A comparison of 5-hydrox-tryptamine receptors mediating contraction in rabbit aorta and dog saphenous veins: Evidence for different receptor types obtained by use of selective agonists and antagonists. Br J Pharmacol 86: 697–704.PubMedCrossRefGoogle Scholar
  77. 76.
    Leysen JE, Awouters F, Kennis L, Laduron PM, Vandenberk J, Janssen PAJ (1981): Receptor binding profile of R41 468, a novel antagonist at 5-HT2 receptors. Life Sci 28: 1015–1022.PubMedCrossRefGoogle Scholar
  78. 77.
    Hoyer D (1985): Characterization of multiple serotonin (5-HT) recognition sites in rat and pig brain membranes by radioligand binding. Naunyn-Schmiedeberg’s Arch Pharmacol 329: R82.Google Scholar
  79. 78.
    Engel G, Göthert M, Hoyer D, Schlicker E, Hillenbrand K (1986): Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg’s Arch Pharmacol 332: 1–7.CrossRefGoogle Scholar
  80. 79.
    Peroutka SJ, Snyder SH, (1979): Multiple serotonin receptors: Differential binding of 3H-5-hydroxytryptamine, 3H-lysergic acid diethylamide and 3H-spiroperidol. Mol Pharmacol 16: 687–699.PubMedGoogle Scholar
  81. 80.
    Taylor EW, Duckies SP, Nelson DL (1986): Dissociation constants of serotonin agonists in the canine basilar artery correlate to K, values at the 5-HT1A binding site. J Pharmacol Exp Ther 236: 118–125.PubMedGoogle Scholar
  82. 81.
    Peroutka SJ, Noguchi M, Tolner DJ, Allen GS (1983): Serotonin-induced contraction of canine basilar artery: Mediation by 5-HT1 receptors. Brain Res 259: 327–330.PubMedCrossRefGoogle Scholar
  83. 82.
    Middlemiss DN, Blakeborough L, Leather SR (1977): Direct evidence for an interaction of β-adrenergic blockers with the 5-HT1 receptor. Nature 267: 289–290.CrossRefGoogle Scholar
  84. 83.
    Middlemiss DN, (1984): Stereospecific blockade at 3H 5-HT binding sites and at 5-HT autoreceptor by propranolol. Eur J Pharmacol 101: 289–293.PubMedCrossRefGoogle Scholar
  85. 84.
    Pazos A, Hoyer D, Palacios JM (1985): The binding of serotonergic ligands to the porcine choroid plexus: Characterization of a new type of serotonin receptor site. Eur J Pharmacol 106: 539–546.CrossRefGoogle Scholar
  86. 85.
    Apperley E, Humphrey PPA (1986): The interaction of 5-hydroxytryptamine and methysergide with methiothepin at “5-HT,-like” receptors in dog saphenous vein. Br J Pharmacol 87:13IP.Google Scholar
  87. 86.
    Cohen RA (1986): Contractions of isolated canine coronary arteries resistant to S2-serotonergic blockade. J Pharmacol Exp Ther 237: 548–552.PubMedGoogle Scholar
  88. 87.
    Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986): Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25: 563–576.PubMedCrossRefGoogle Scholar
  89. 88.
    Chang J-Y, Owman Ch (1989): Serotonin potentiates noradrenaline-induced vasoconstriction through 5-HT1, type receptors in guinea-pig basilar artery. J Cereb. Blood Flow Metab 9: 713–716.PubMedCrossRefGoogle Scholar
  90. 89.
    Apperley E, Feniuk W, Humphrey PPA, Levy GP (1980): Evidence for two types of 3H-5-hydroxytryptamine uptake within rat cerebrovascular tree. Eur J Pharmacol 112: 181–186.Google Scholar
  91. 90.
    Peroutka SJ (1984): 5-HT receptor sites and functional correlates. Neuropharmacology 23:1489–1492.CrossRefGoogle Scholar
  92. 91.
    Saxena PR (1972): The effects of antimigraine drugs on the vascular response by 5-hydroxytryptamine and related biogenic substances on the external carotid bed of dog: Possible pharmacological implications to their antimigraine action. Headache 12: 44–54.PubMedCrossRefGoogle Scholar
  93. 92.
    Carroll PR, Ebeling PW, Glover WE (1974): The responses of the human temporal and rabbit ear artery to 5-hydroxytryptamine and some of its antagonists. Aust J Exp Biol Med Sci 52: 813–823.PubMedCrossRefGoogle Scholar
  94. 93.
    Tsuji T, Chiba S (1984): Potentiating effect of methysergide on norepinephrine-induced constriction of isolated internal carotid artery of the dog. Japan J Pharmacol 34: 95–100.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1990

Authors and Affiliations

  • Christer Owman
  • Jing-Yu Chang
  • Jan Erik Hardebo

There are no affiliations available

Personalised recommendations