Article date: July 1994
By: Valérie Deckert, Didier Pruneau, Jean‐Luc Elghozi, in Volume 112, Issue 3, pages 939-945
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.
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.
The selective antagonists of 5‐HT2A/2C (ketanserin), 5‐HT4 (SDZ 205–557) and 5‐HT1A/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.
In both arteries, the contraction‐response curve to 5‐HT was unaffected by the 5‐HT3 receptor antagonist, ICS 205–930 (0.01 and 0.1 μm) whilst a small (3 and 6 fold displacement) was seen with MDL 72222 (0.1 and 1 μm).
The mixed 5‐HT1‐like/5‐HT2A receptor antagonist, methiothepin (0.001–0.1 μm), was a potent antagonist of 5‐HT‐induced contractions in both arteries, giving pA2 values of 9.4 ± 0.7 and 9.6 ± 0.8 in MCA and PCA, respectively.
Rauwolscine (0.1–10 μm) and yohimbine (0.3, 3 μm) inhibited contractions to 5‐HT in a competitive manner, pA2 values of 7.1 ± 0.6 and 6.7 ± 0.6 were determined for rauwolscine in MCA and PCA, respectively. An apparent pA2 value of 6.9 ± 0.2 was calculated for yohimbine (3 μm) in both MCA and PCA.
In conclusion, these results suggest that the contractile response to 5‐HT in rabbit isolated MCA and PCA is predominantly mediated by the 5‐HT1D receptor subtype, although a small contribution by 5‐HT3 receptors cannot be excluded.
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.
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.
The selective antagonists of 5‐HT2A/2C (ketanserin), 5‐HT4 (SDZ 205–557) and 5‐HT1A/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.
In both arteries, the contraction‐response curve to 5‐HT was unaffected by the 5‐HT3 receptor antagonist, ICS 205–930 (0.01 and 0.1 μm) whilst a small (3 and 6 fold displacement) was seen with MDL 72222 (0.1 and 1 μm).
The mixed 5‐HT1‐like/5‐HT2A receptor antagonist, methiothepin (0.001–0.1 μm), was a potent antagonist of 5‐HT‐induced contractions in both arteries, giving pA2 values of 9.4 ± 0.7 and 9.6 ± 0.8 in MCA and PCA, respectively.
Rauwolscine (0.1–10 μm) and yohimbine (0.3, 3 μm) inhibited contractions to 5‐HT in a competitive manner, pA2 values of 7.1 ± 0.6 and 6.7 ± 0.6 were determined for rauwolscine in MCA and PCA, respectively. An apparent pA2 value of 6.9 ± 0.2 was calculated for yohimbine (3 μm) in both MCA and PCA.
In conclusion, these results suggest that the contractile response to 5‐HT in rabbit isolated MCA and PCA is predominantly mediated by the 5‐HT1D receptor subtype, although a small contribution by 5‐HT3 receptors cannot be excluded.
DOI: 10.1111/j.1476-5381.1994.tb13171.x
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