Inhibition of tryptophan hydroxylase abolishes fatigue induced by central tryptophan in exercising rats

Add time:09/29/2019    Source:infona.pl

Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (TRP) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (p‐CPA), an inhibitor of the conversion of TRP to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (ip) injections of saline or p‐CPA. On the day of the experiment, animals received intracerebroventricular (icv) injections of either saline or TRP (20.3 μM) and underwent a submaximal exercise test until fatigue. Icv TRP‐treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip p‐CPA blocked the effects of TRP on thermoregulation and performance. Moreover, ip p‐CPA administration accelerated cutaneous heat dissipation when compared with saline‐pretreated rats. We conclude that an elevated availability of central TRP interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because TRP effects were blocked in the presence of p‐CPA. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise.

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Prev:Modulation of ligand selectivity by mutation of the first extracellular loop of the human C5a receptor11Abbreviations: C5aR, human complement fragment 5a receptor; WT, wild-type; G105D, C5aR mutated to aspartate at glycine105; P103Y, C5aR mutated to tyrosine at proline105; P103Y/G105D, C5aR containing both substitutions; C5adR74, des arginated C5a; F-[OPchaWR], phenylalanine [l-ornithine-proline-d-cyclohexylalanine-tryptophan-arginine]; MeFKPchaWr, N-methyl-l-phenylalanine-lysine-proline-d-cyclohexylalanine-tryptophan-d-arginine; PMN, polymorphonuclear leukocytes; PCR, polymerase chain reaction; YSFKPMPLaR, l-tyrosine-serine-phenylalanine-lysine-proline-methionine-proline-leucine-d-alanine-arginine; and YSFKD(MeNle)PIAR, l-tyrosine-serine-phenylalanine-lysine-aspartate-N-methylnorleucine-proline-d-leucine-alanine-arginine.
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