Premium
Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y
Author(s) -
Taksande BG,
Kotagale NR,
Nakhate KT,
Mali PD,
Kokare DM,
Hirani K,
Subhedar NK,
Chopde CT,
Ugale RR
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01484.x
Subject(s) - neuropeptide y receptor , endocrinology , neuropeptide , hypothalamus , agmatine , medicine , nucleus , neuroscience , chemistry , biology , biochemistry , receptor , amino acid , arginine
BACKGROUND AND PURPOSE Agmatine, a multifaceted neurotransmitter, is abundantly expressed in the hypothalamic paraventricular nucleus (PVN). Our aim was to assess (i) the effect of agmatine on feeding behaviour and (ii) its association, if any, with neuropeptide Y (NPY). EXPERIMENTAL APPROACH Satiated rats fitted with intra‐PVN cannulae were administered agmatine, alone or jointly with (i) α 2 ‐adrenoceptor agonist, clonidine, or antagonist, yohimbine; (ii) NPY, NPY Y 1 receptor agonist, [Leu 31 , Pro 34 ]‐NPY, or antagonist, BIBP3226; or (iii) yohimbine and NPY. Cumulative food intake was monitored at different post‐injection time points. Furthermore, the expression of hypothalamic NPY following i.p. treatment with agmatine, alone or in combination with yohimbine (i.p.), was evaluated by immunocytochemistry. KEY RESULTS Agmatine robustly increased feeding in a dose‐dependent manner. While pretreatment with clonidine augmented, yohimbine attenuated the orexigenic response to agmatine. Similarly, NPY and [Leu 31 , Pro 34 ]‐NPY potentiated the agmatine‐induced hyperphagia, whereas BIBP3226 inhibited it. Moreover, yohimbine attenuated the synergistic orexigenic effect induced by the combination of NPY and agmatine. Agmatine increased NPY immunoreactivity in the PVN fibres and in the cells of the hypothalamic arcuate nucleus (ARC) and this effect was prevented by pretreatment with yohimbine. NPY immunoreactivity in the fibres of the ARC, dorsomedial, ventromedial and lateral nuclei of the hypothalamus was not affected by any of the above treatments. CONCLUSIONS AND IMPLICATIONS The orexigenic effect of agmatine is coupled to increased NPY activity mediated by stimulation of α 2 ‐adrenoceptors within the PVN. This signifies the importance of agmatine or α 2 ‐adrenoceptor modulators in the development of novel therapeutic agents to treat feeding‐related disorders.