No hypothermic response to serotonin in 5-HT7 receptor knockout mice.
With data from recently available selective antagonists for the 5-HT(7) receptor, it has been hypothesized that 5-hydroxytryptamine (5-HT)-induced hypothermia is mediated by the 5-HT(7) receptor, an effect previously attributed to other receptor subtypes. It has been established that the biologically active lipid oleamide allosterically interacts with the 5-HT(7) receptor to regulate its transmission. The most well characterized effects of oleamide administration are induction of sleep and hypothermia. Here, we demonstrate, by using mice lacking the 5-HT(7) receptor, that 5-HT-induced hypothermia is mediated by the 5-HT(7) receptor. Both 5-HT and 5-carboxamidotryptamine, a 5-HT(1) and 5-HT(7) receptor agonist, in physiological doses fail to induce hypothermia in 5-HT(7) knockout mice. In contrast, oleamide was equally effective in inducing hypothermia in mice lacking the 5-HT(7) receptors as in wild-type mice. When administered together, 5-HT and oleamide showed additive or greater than additive effects in reducing body temperature. Taken together, the results show that 5-HT-induced hypothermia is mediated by the 5-HT(7) receptor, and that oleamide may act through an independent mechanism as well as at an allosteric 5-HT(7) receptor site to regulate body temperature.
Hedlund
P B
PB
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Danielson
P E
PE
Thomas
E A
EA
Slanina
K
K
Carson
M J
MJ
Sutcliffe
J G
JG
D000495:Allosteric Site; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007035:Hypothermia; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009829:Oleic Acids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics* / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
D006993:Hypnotics and Sedatives; D009829:Oleic Acids; D016760:Proto-Oncogene Proteins c-fos; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D012701:Serotonin; C029407:oleylamide; C047087:5-carboxamidotryptamine; D000242:Cyclic AMP