In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 284, No. 6 ( 2003-06-01), p. R1595-R1603
Abstract:
Activation of central melanocortin receptors (MCR) inhibits fever, but the identity of the MCR subtype(s) mediating this antipyretic effect is unknown. To determine whether selective central melanocortin receptor-4 (MC4R) activation produces antipyretic effects, the MC4R selective agonist MRLOB-0001 (CO-His-d-Phe-Arg-Trp-Dab-NH 2 ) was administered intracerebroventricularly to rats treated with Escherichia coli lipopolysaccharide (LPS, 30 μg/kg ip). Treatment with MRLOB-0001 (150 ng icv) did not lower core body temperature (T c ) in afebrile rats but did suppress LPS-induced increases in T c and associated decreases in tail skin temperature (T sk ), an indicator of vasomotor thermoeffector function. In contrast, systemic treatment with MRLOB-0001 (150 ng iv) did not produce similar antipyretic effects. Coadministration of the selective MC4R antagonist HS014 (1 μg icv) blocked the antipyretic effects of MRLOB-0001. HS014 alone (1 μg icv) had no significant effect on LPS-induced increases in T c or decreases in T sk and in afebrile rats had no significant effects on T c or T sk . We conclude that pharmacological activation of central MC4R suppresses febrile increases in T c and that inhibition of heat conservation pathways may contribute to this effect. These findings suggest that the central MC4R may mediate the long-recognized antipyretic effects of centrally administered melanocortins.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.00581.2002
Language:
English
Publisher:
American Physiological Society
Publication Date:
2003
detail.hit.zdb_id:
1477297-8
SSG:
12
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