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Enhanced food intake after stimulation of hypothalamic P2Y 1 receptors in rats: modulation of feeding behaviour by extracellular nucleotides
Author(s) -
Kittner Holger,
Franke Heike,
Harsch Julia I.,
ElAshmawy Ibrahim M.,
Seidel Bertholt,
Krügel Ute,
Illes Peter
Publication year - 2006
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 - 10.1111/j.1460-9568.2006.05071.x
Subject(s) - ppads , p2y receptor , p2 receptor , medicine , endocrinology , receptor , stimulation , purinergic receptor , adenosine , receptor antagonist , nitric oxide synthase , extracellular , hypothalamus , biology , antagonist , chemistry , nitric oxide , biochemistry
The present study was aimed to clarify the role of purinergic signalling in the regulation of ingestion behaviour. The ATP/ADP analogues 2‐methylthioATP (2‐MeSATP) and adenosine 5′‐O‐(2‐thiodiphosphate) (ADPβS) increased the food intake after intracerebroventricular infusion in 18‐h food‐deprived rats. This effect was abolished by pretreatment with the non‐selective P2X/P2Y receptor antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) or the selective P2Y 1 receptor antagonist MRS 2179, respectively. The stimulation of food intake mediated by ADPβS was also blocked by pretreatment with the nitric oxide synthase (NOS) inhibitor N w ‐nitro‐ l ‐arginine methylester (L‐NAME), as well as with the inhibitor of the soluble guanylyl cyclase 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), suggesting that the orexigenic effect seems to be closely related with the ensuing formation of nitric oxide. The immunohistochemical staining indicating a co‐localization of P2Y 1 receptor‐ and nNOS‐immunoreactivities in a population of neurons in the ventromedial hypothalamic nucleus (VMH) agrees with this assumption. Further experiments with the direct local application of these compounds into the VMH and lateral hypothalamic nucleus (LH) show that the stimulation of P2Y 1 receptors in these functionally antagonistic brain regions exerts an increased food intake. Hence, different signal transduction mechanisms may operate in the VMH and LH. Our assumption is supported by distinct effects of the NOS inhibitor L‐NAME in these two hypothalamic nuclei. The present data suggest that ATP/ADP, acting as extracellular signal molecules in the rat brain, are involved in the regulation of food intake, possibly depending on P2Y 1 ‐receptor‐mediated nitric oxide production.