Thermogenic actions of tryptophan in the rat are mediated independently of 5-HT.
Serotonin (5-HT) has been implicated in the central control of energy balance, via inhibition of food intake and stimulation of thermogenesis. Its rate of synthesis in brain is dependent on the availability of its precursor amino acid, tryptophan. The objective of the present study was therefore to investigate the thermogenic actions of tryptophan and to determine whether these actions are mediated by 5-HT. Central or peripheral injections of 5-HT (i.c.v.; 0.5-40 micrograms), 5-hydroxytryptophan (5-HTP) (i.c.v.; 20 micrograms) or tryptophan (i.p.; 20 mg/kg, i.c.v.; 12-60 micrograms) significantly increased resting oxygen consumption (VO2 by approximately 15-20%) in conscious rats, without apparent effects on physical activity. Small increases (5-7%) in VO2 were also observed following peripheral injections of aspartate or glycine (20 mg/kg) but not taurine, whilst central injections of tyrosine or leucine (15-18 micrograms) significantly increased VO2 by 15%. We have previously reported that the thermogenic and anorexic actions of 5-HT are mediated by corticotropin-releasing factor (CRF). In the present study, the thermogenic actions of 5-HTP, like those of 5-HT, were significantly reduced by pretreatment (5 min before) with the CRF antagonist alpha-helical CRF9-41 (25 micrograms, i.c.v.) or a polyclonal antibody to CRF. However, the thermogenic actions of tryptophan were not significantly modified by pretreatment with either the 5-HT antagonist, methysergide (20 micrograms, i.c.v.) or with the CRF antagonist or antibody and thus appear to act through different mechanisms to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Serra
F
F
Departamento de Biologia Fonamental i Ciències de la Salut, University of Illes Balears, Palma de Mallorca, Spain.
LeFeuvre
R A
RA
Slater
D
D
Palou
A
A
Rothwell
N J
NJ
D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000494:pharmacology*; D000596:Amino Acids / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D014364:Tryptophan / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism
D000596:Amino Acids; D010446:Peptide Fragments; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D014364:Tryptophan; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D006916:5-Hydroxytryptophan