5-Hydroxytryptamine Receptors Mediating Carotid and Systemic Haemodynamic Effects: The Relation to Acute Antimigraine Therapy

The presence of a vasoconstrictor substance in blood was suspected for 130 years (Ludwig & Schmidt, 1868) and, 50 years ago, Page and associates at the Cleveland Clinic (Cleveland, Ohio, USA) succeeded in isolating 'serotonin' from the blood (Rapport et al., 1948). Within the next 3 years, the chemical structure of serotonin was deduced (Rapport, 1949) and 5-HT (5-hydroxytryptamine; for other abbreviations see Section 16.4) synthesised (Hamlin & Fischer, 1951; Speeter et al., 1951). Independently, during the 1930s and 40s, Erspamer and colleagues (Rome, Italy), who were interested in characterising the substance imparting characteristic histochemical properties to the enterochromaffin cells of the gastrointestinal mucosa, extracted a basic gut-stimulating factor and named it "enteramine" (Erspamer, 1954). The chemical identity of enteramine with the natural and synthetic serotonin (Erspamer & Asero, 1952) was soon backed by the similarity of pharmacological profile (contraction of sheep carotid artery, guinea-pig, mouse and rabbit jejunum, rat and cat uterus and cat nictitating membrane, triphasic blood pressure response and antagonism by yohimbine and potentiation by cocaine of the sheep carotid artery contraction) (Erspamer, 1954; Page, 1954). Thus, the scene was set for the characterisation of 5-HT receptors.

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