Involvement of 5-HT1B receptors in collar-induced hypersensitivity to 5-hydroxytryptamine of the rabbit carotid artery.
In humans intimal thickening is aprerequisite 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.
Geerts
I S
IS
Laboratory of Pharmacology, Faculty of Medicine and Pharmaceutical Sciences, University of Antwerp UIA, Wilrijk, Belgium. igeerts@uia.ac.be
Matthys
K E
KE
Herman
A G
AG
Bult
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001915:Braces / Q000009:adverse effects*; D002339:Carotid Arteries / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006967:Hypersensitivity / Q000209:etiology*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D010069:Oxadiazoles; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C085632:L 694247; D016713:Ritanserin; D012701:Serotonin; D013134:Spiperone; D011189:Potassium Chloride; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D008784:Methysergide