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Mediation by 5‐HT 1D receptors of 5‐hydroxytryptamine‐induced contractions of rabbit middle and posterior cerebral arteries
Author(s) -
Deckert Valérie,
Pruneau Didier,
Elghozi JeanLuc
Publication year - 1994
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.1476-5381.1994.tb13171.x
Subject(s) - ketanserin , 5 ht receptor , medicine , endocrinology , cerebral arteries , receptor antagonist , contraction (grammar) , receptor , 5 ht1 receptor , serotonin , antagonist , chemistry , biology
1 5‐Hydroxytryptamine (5‐HT) receptor‐mediated contraction of endothelium denuded rabbit middle (MCA) and posterior (PCA) cerebral arteries was characterized by use of selective agonists and antagonists for different 5‐HT receptor subtypes. 2 5‐HT and various 5‐HT receptor agonists contracted the arteries with the following rank order of potency in MCA: 5‐carboxamidotryptamine (5‐CT) > 5‐HT > 5‐methoxytryptamine (5‐MeOT) > sumatriptan > α‐methyl‐5‐HT (α‐Me‐5‐HT) >> 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and in PCA: 5‐CT > 5‐HT >sumatriptan > 5‐MeOT > α‐Me‐5‐HT >> 8‐OH‐DPAT. With few exceptions, the maximal contractile responses of these agonists were similar to that induced by 5‐HT. 3 The selective antagonists of 5‐HT 2A/2C (ketanserin), 5‐HT 4 (SDZ 205–557) and 5‐HT 1A/1B (S‐(−)‐propranolol) sites were devoid of inhibitory effect on 5‐HT‐mediated contraction in both MCA and PCA, thus excluding activation of the corresponding receptors. 4 In both arteries, the contraction‐response curve to 5‐HT was unaffected by the 5‐HT 3 receptor antagonist, ICS 205–930 (0.01 and 0.1 μ m ) whilst a small (3 and 6 fold displacement) was seen with MDL 72222 (0.1 and 1 μ m ). 5 The mixed 5‐HT 1 ‐like/5‐HT 2A receptor antagonist, methiothepin (0.001–0.1 μ m ), was a potent antagonist of 5‐HT‐induced contractions in both arteries, giving pA 2 values of 9.4 ± 0.7 and 9.6 ± 0.8 in MCA and PCA, respectively. 6 Rauwolscine (0.1–10 μ m ) and yohimbine (0.3, 3 μ m ) inhibited contractions to 5‐HT in a competitive manner, pA 2 values of 7.1 ± 0.6 and 6.7 ± 0.6 were determined for rauwolscine in MCA and PCA, respectively. An apparent pA 2 value of 6.9 ± 0.2 was calculated for yohimbine (3 μ m ) in both MCA and PCA. 7 In conclusion, these results suggest that the contractile response to 5‐HT in rabbit isolated MCA and PCA is predominantly mediated by the 5‐HT 1D receptor subtype, although a small contribution by 5‐HT 3 receptors cannot be excluded.