EVIDENCE FOR TWO TYPES OF EXCITATORY RECEPTOR FOR 5‐HYDROXYTRYPTAMINE IN DOG ISOLATED VASCULATURE

Abstract

As part of an investigation into the mode of action of anti‐migraine drugs, a study of the excitatory receptors for 5‐hydroxytryptamine (5‐HT) has been carried out in a range of isolated vascular preparations from the dog. 5‐HT contracted the dog isolated femoral artery and saphenous vein over the concentration‐range 1.0 × 10⁻⁸to 5.0 × 10⁻⁶mol/l. In the femoral artery methysergide and cyproheptadine were potent, competitive and specific antagonists of the contractile responses to 5‐HT, with pA₂ values of 8.52 and 8.55 respectively. In the saphenous vein, methysergide was only a weak antagonist of 5‐HT. In addition, it was an agonist over the concentration‐range 5.0 × 10⁻⁸to 1.0 × 10⁻⁵mol/l. Cyproheptadine was a weak and unsurmountable antagonist of contractile responses to 5‐HT and methysergide. Contractile responses to 5‐HT and methysergide in the saphenous vein were not antagonized by morphine (3.0 × 10⁻⁵mol/l), indomethacin (5.0 × 10⁻⁵mol/l), phentolamine (5.0 × 10⁻⁷mol/l), propranolol (1.0 × 10⁻⁶mol/l), atropine (1.0 × 10⁻⁶mol/l), mepyramine (1.0 × 10⁻⁶mol/l) or cimetidine (1.0 × 10⁻⁵mol/l). In the external carotid and lingual arteries the pattern of activity obtained with methysergide and cyproheptadine was the same as that in the femoral artery, while in the auricular artery the pattern of activity was the same as that in the saphenous vein. The results are consistent with the hypothesis that there are two types of receptor mediating 5‐HT‐induced vasoconstriction in dog vasculature. One type, characterized by the pattern of activity obtained in the femoral artery, is like the previously described ‘D‐receptor’. The other type, characterized by the pattern of activity obtained in the saphenous vein, has not been described before. The verification of this hypothesis requires the identification of a specific antagonist of 5‐HT and methysergide in the saphenous vein.