Vasoconstrictor effects of various melatonin analogs on the rat tail artery in the presence of phenylephrine.
We performed a pharmacologic analysis of the increase in perfusion pressure induced by melatonin and related analogues in the perfused rat tail artery precontracted by 1 microM phenylephrine. Melatonin, 2-iodomelatonin, 6-chloromelatonin, and S20098 (N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide) produced a concentration-dependent enhancement of the vasoconstrictor response evoked by 1 microM phenylephrine with a rank order of potency compatible with the pharmacologic profile defined for high-affinity melatonin receptors. Melatonin had no effect on electrically induced [3H]noradrenaline release, but the neurogenic vasoconstriction was increased at melatonin concentrations of 100 and 300 nM. Increasing concentrations of the naphthalenic-based antagonist S20928 (N-[2-(1-naphthyl)ethyl]cyclobutanecarboxamide) caused a parallel rightward shift in the melatonin concentration-response curve without depressing the maximal response. The pA2 value of S20928 was 7.01 +/- 0.08. Luzindole, 1 microM, an antagonist of Mel1b melatonin receptors, was without effect on melatonin-induced responses. By using reverse transcription-polymerase chain reaction (RT-PCR), we found that messenger RNA (mRNA) encoding for Mel1a is transcribed in the rat tail artery. In conclusion, the results show that melatonin produced an enhancement of the contractile response elicited by phenylephrine in the perfused rat tail artery. This vasoconstrictor response appears to be mediated through activation of Mel1a receptors located on smooth-muscle cells. No evidence for an action of melatonin on either the endothelium or sympathetic nerve endings was found.
Laboratoire de Pharmacologie et Physiologie Cellulaires, C.N.R.S. ERS 653, Université Louis Pasteur Strasbourg, Illkirch, France.
B
B
Bucher
F
F
Gauer
P
P
Pévet
M
M
Masson-Pévet
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004727:Endothelium / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009130:Muscle, Smooth / Q000502:physiology; D009411:Nerve Endings / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D044094:Receptors, Melatonin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013564:Sympathetic Nervous System / Q000187:drug effects; D013623:Tail / Q000098:blood supply*; D014363:Tryptamines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D009281:Naphthalenes
D000081:Acetamides; D008550:Melatonin; D009638:Norepinephrine; D010656:Phenylephrine; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; C084711:agomelatine; D009281:Naphthalenes; C024100:6-chloromelatonin; C044556:2-iodomelatonin