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Vascular 5‐HT 1 ‐like receptors mediating vasoconstriction and vasodilatation: their characterization and distribution in the intact canine cardiovascular system
Author(s) -
Cambridge D.,
Whiting M.V.,
Butterfield L.J.,
Marston C.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13298.x
Subject(s) - ketanserin , vasodilation , vasoconstriction , 5 ht receptor , spiperone , potency , agonist , serotonin , medicine , endocrinology , serotonin antagonists , receptor , pharmacology , ritanserin , chemistry , biochemistry , in vitro
1 In anaesthetized dogs, intra‐left atrial administration of 5‐hydroxytryptamine (5‐HT) and selected tryptamine analogues (5‐carboxamidotryptamine, 5‐CT; 5‐methyl tryptamine, 5‐MT; α‐methyl 5‐hydroxytryptamine, α‐HT; sumatriptan, Sum) in the presence of ketanserin and MDL72222 (5‐HT 2 and 5‐HT 3 receptor antagonists, respectively), produced dose‐related changes in carotid, coronary and renal vascular conductance mediated by vascular 5‐HT 1 ‐like receptors. 2 In the carotid vascular bed, 5‐HT, 5‐MT, α‐HT and Sum were vasoconstrictors with a rank order of potency (comparing ED 50 values) of 5‐HT = Sum > 5‐MT > α‐HT. By contrast in this vascular bed, 5‐CT was a potent vasodilator. 3 In the coronary vascular bed, 5‐HT, 5‐CT, 5‐MT and α‐HT were vasodilators with a rank order of potency (comparing ED 50 values) of 5‐CT > 5‐HT > 5‐MT > α‐HT. In this vascular bed, Sum was without effect. 4 In the renal vascular bed, 5‐HT, 5‐CT, 5‐MT, α‐HT and Sum were vasoconstrictors with a rank order of potency (comparing ED 50 values) of 5‐CT > 5‐HT > Sum> 5‐MT > α‐HT. 5 The coronary (and carotid) vasodilator responses to 5‐CT were antagonized by the 5‐HT 1 ‐like receptor antagonists, spiperone (1 mg kg −1 ) and methiothepin (0.1 mg kg −1 ), whereas the renal vasoconstrictor responses to this tryptamine analogue were antagonized only by methiothepin. 6 It is concluded from these studies that agonist finger‐printing in vivo , using tryptamine analogues, identifies and confirms the functional presence of at least two pharmacologically distinct subtypes of the 5‐HT 1 ‐like receptor in the intact canine cardiovascular system. These two subtypes are located on the vascular smooth muscle and mediate direct vasoconstriction and vasodilatation responses in vivo . 7 In addition, these studies confirm that the distribution of these subtypes within the major vascular beds, shows a marked heterogeneity. The carotid vascular responses to the tryptamine analogues indicate the presence of both the vasodilator and the vasoconstrictor subtypes. The coronary vascular responses to these analogues are, however, consistent with presence of the vasodilator subtype, only. By contrast, the renal vascular responses to these analogues indicates only the presence of the vasoconstrictor subtype.