Involvement of 5-HT(1B) receptors in collar-induced hypersensitivity to 5-hydroxytryptamine of the rabbit carotid artery

1. 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. 2. 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. 3. Collared rings were more sensitive to the contractile effect of 5-HT (7.6 fold) and 5-carboxamidotryptamine (31 fold, 5-CT, 5-HT(1) agonist) in cumulative concentration response curves. Sumatriptan (5-HT(1B/1D) agonist) caused concentration-dependent constrictions in collared rings only. 4. Collar placement did not significantly alter pA(2) values (Schild regression) or apparent pK(b) values (non-linear regression) of spiperone and methysergide (mixed 5-HT(2A)/5-HT(1) antagonists) or ketanserin and ritanserin (5-HT(2A) antagonists), indicating unchanged binding characteristics of the 5-HT(2A) receptor. However, the reduced slope of the Schild regression pointed to a heterogeneous receptor population in collared rings. 5. In contrast, the apparent pK(b) value of methiothepin (5-HT(1B) antagonist) was significantly reduced by collar placement, and its antagonism shifted from non-surmountable in sham rings to surmountable in collared segments. 6. Taken together, this study demonstrates that the serotonergic receptor involved in the hypersensitivity to 5-HT of rabbit collared carotid artery is a 5-HT(1B) receptor subtype