Collar-induced elevation of mRNA and functional activity of 5-HT1B receptor in the rabbit carotid artery

1 Hypersensitivity to serotonin (5-HT) develops in rabbit collared carotid arteries. Previous data demonstrated the involvement of 5-HT1-like receptor s which are not active in normal carotid arteries. This study investigated the interaction in the rabbit carotid artery between 5-HT and a moderate to ne as this can uncover functional 5-HT1-like receptors. Furthermore, the ex pression of messenger RNA (mRNA) and protein of 5-HT1B, 5-HT1D and 5-HT2A r eceptors was addressed. 2 Silicone collars were placed around the carotid arteries of male New Zeal and White rabbits for 1 week. Rings from inside (= collar) and outside (= s ham) the collar were either mounted in isolated organ baths for isometric f orce measurements or frozen in liquid nitrogen to isolate total RNA or prot eins which were subsequently analysed by respectively reverse transcriptase -polymerase chain reaction and Western blot analysis. 3 In sham and collared rings concentration-response curves (CRC's) to 5-HT were monophasic. Only in collared segments the presence of a 5-HT2A antagon ist (spiperone or ketanserin, 0.1 muM) revealed a biphasic CRC which was ev en more pronounced when a moderate tone was induced by KCl pointing to func tional 5-HT1-like receptors. 4 The rabbit carotid artery constitutively expressed 5-HT1B and 5-HT2A mRNA , not 5-HT1D mRNA. Manipulation of the carotid artery increased the 5-HT1B mRNA level. Collar placement raised it even further. The 5-HT2A mRNA level remained unchanged. All the anti-5-HT receptor antibodies tested resulted i n variable, non specific patterns with multiple bands. 5 In conclusion, collar placement elevates mRNA expression and activity of the 5-HT1B receptor in the rabbit carotid artery.