Article date: July 1999
By: Inge S Geerts, Katelijne E Matthys, Arnold G Herman, Hidde Bult, in Volume 127, Issue 6, pages 1327-1336
In humans intimal thickening is a prerequisite of atherosclerosis. Application of a silicone collar around the rabbit carotid artery induces an intimal thickening but in addition it increases the sensitivity to the vasoconstrictor action of serotonin (5‐hydroxytryptamine, 5‐HT). The 5‐HT receptors involved in collar‐induced hypersensitivity to 5‐HT were investigated using several agonists and antagonists.
One week after placement of collars around both carotid arteries of anaesthetized rabbits, rings (2 mm width) from inside (=collar) and outside (=sham) the collars were mounted in organ baths (10 ml) for isometric force measurements at 6 g loading tension.
Collared rings were more sensitive to the contractile effect of 5‐HT (7.6 fold) and 5‐carboxamidotryptamine (31 fold, 5‐CT, 5‐HT1 agonist) in cumulative concentration response curves. Sumatriptan (5‐HT1B/1D agonist) caused concentration‐dependent constrictions in collared rings only.
Collar placement did not significantly alter pA2 values (Schild regression) or apparent pKb values (non‐linear regression) of spiperone and methysergide (mixed 5‐HT2A/5‐HT1 antagonists) or ketanserin and ritanserin (5‐HT2A antagonists), indicating unchanged binding characteristics of the 5‐HT2A receptor. However, the reduced slope of the Schild regression pointed to a heterogeneous receptor population in collared rings.
In contrast, the apparent pKb value of methiothepin (5‐HT1B antagonist) was significantly reduced by collar placement, and its antagonism shifted from non‐surmountable in sham rings to surmountable in collared segments.
Taken together, this study demonstrates that the serotonergic receptor involved in the hypersensitivity to 5‐HT of rabbit collared carotid artery is a 5‐HT1B receptor subtype.
In humans intimal thickening is a prerequisite of atherosclerosis. Application of a silicone collar around the rabbit carotid artery induces an intimal thickening but in addition it increases the sensitivity to the vasoconstrictor action of serotonin (5‐hydroxytryptamine, 5‐HT). The 5‐HT receptors involved in collar‐induced hypersensitivity to 5‐HT were investigated using several agonists and antagonists.
One week after placement of collars around both carotid arteries of anaesthetized rabbits, rings (2 mm width) from inside (=collar) and outside (=sham) the collars were mounted in organ baths (10 ml) for isometric force measurements at 6 g loading tension.
Collared rings were more sensitive to the contractile effect of 5‐HT (7.6 fold) and 5‐carboxamidotryptamine (31 fold, 5‐CT, 5‐HT1 agonist) in cumulative concentration response curves. Sumatriptan (5‐HT1B/1D agonist) caused concentration‐dependent constrictions in collared rings only.
Collar placement did not significantly alter pA2 values (Schild regression) or apparent pKb values (non‐linear regression) of spiperone and methysergide (mixed 5‐HT2A/5‐HT1 antagonists) or ketanserin and ritanserin (5‐HT2A antagonists), indicating unchanged binding characteristics of the 5‐HT2A receptor. However, the reduced slope of the Schild regression pointed to a heterogeneous receptor population in collared rings.
In contrast, the apparent pKb value of methiothepin (5‐HT1B antagonist) was significantly reduced by collar placement, and its antagonism shifted from non‐surmountable in sham rings to surmountable in collared segments.
Taken together, this study demonstrates that the serotonergic receptor involved in the hypersensitivity to 5‐HT of rabbit collared carotid artery is a 5‐HT1B receptor subtype.
British Journal of Pharmacology (1999) 127, 1327–1336; doi:10.1038/sj.bjp.0702684
DOI: 10.1038/sj.bjp.0702684
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