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Hypocretin‐1 causes G protein activation and increases ACh release in rat pons
Author(s) -
Bernard René,
Lydic Ralph,
Baghdoyan Helen A.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02905.x
Subject(s) - pons , neuroscience , acetylcholine , chemistry , microbiology and biotechnology , biophysics , psychology , endocrinology , biology
The effects of the arousal‐promoting peptide hypocretin on brain stem G protein activation and ACh release were examined using 16 adult Sprague‐Dawley rats. In vitro [ 35 S]GTPγS autoradiography was used to test the hypothesis that hypocretin‐1‐stimulated G protein activation is concentration‐dependent and blocked by the hypocretin receptor antagonist SB‐334867. Activated G proteins were quantified in dorsal raphe nucleus (DR), locus coeruleus (LC) and pontine reticular nucleus oral part (PnO) and caudal part (PnC). Concentration–response data revealed a significant ( P < 0.001) effect of hypocretin‐1 (2–2000 n m ) in all brain regions examined. Maximal increases over control levels of [ 35 S]GTPγS binding were 37% (DR), 58% (LC), 52% (PnO) and 44% (PnC). SB‐334867 (2 µ m ) significantly ( P < 0.002) blocked hypocretin‐1 (200 n m )‐stimulated [ 35 S]GTPγS binding in all four nuclei. This is the first autoradiographic demonstration that hypocretin‐1 activates G proteins in arousal‐related brain stem nuclei as a result of specific receptor interactions. This finding suggests that some hypocretin receptors in brain stem couple to inhibitory G proteins. In vivo microdialysis was used to test the hypothesis that PnO administration of hypocretin‐1 increases ACh release in PnO. Dialysis delivery of hypocretin‐1 (100 µ m ) significantly ( P < 0.002) increased (87%) ACh release. This finding is consistent with the interpretation that one mechanism by which hypocretin promotes arousal is by enhancing cholinergic neurotransmission in the pontine reticular formation.