The possible existence of extrapituitary melanocyte stimulating hormone (MSH) in various regions of the rat brain has been studied in intact and hypophysectomized rats. Using a sensitive and specific radioimmunoassay (RIA), αMSH has been found in a number of brain regions in intact rats. The standard curves of synthetic αMSH and the dilution curves for pars intermedia nervosa (PIN), pars distalis (PD), hypothalamus and thalamus extracts were strictly parallel. The αMSH concentrations were measured in PIN (6,225 ± 962 ng/mg wet tissue); PD (12.5 ± 1.41 ng/mg); pineal (380 ± 29 ng/g wet tissue); hypothalamus (645 ± 161 ng/g) and thalamus (33.3 ± 5.26 ng/g). In rats hypophysectomized for 1 or 2 months, the highest concentrations of immunoreactive αMSH were found in pineal (353 ± 140 ng/g wet tissue), hypothalamus (85.8 ±14.1 ng/g) and thalamus (39.8 ± 13.9 ng/g). Hypophysectomy significantly reduced hypothalamic MSH content and concentration but did not alter MSH concentration in pineal and thalamus. From these results, we conclude that hypothalamic αMSH is, in part, of hypophyseal origin while pineal and thalamus «MSH does not originate from the pituitary. After Sephadex G-25 gel filtration, synthetic αMSH and PIN extracts showed a single peak of both bioactive and immunoreactive αMSH. In the same conditions, extracts from the 5 brain regions studied in hypophysectomized rats chromatographed as a single peak of immunoreactive MSH but as 2 peaks of apparent bioactive MSH, 1 concident with synthetic αMSH and the other far after the salt volume. We conclude that αMSH is found in a number of brain areas and its presence after hypophysectomy would indicate synthesis within the central nervous system.
UII (urotensin II) and its paralogue URP (UII-related peptide) are two vasoactive neuropeptides whose respective central actions are currently unknown. In the present study, we have compared the mechanism of action of URP and UII on cultured astrocytes. Competition experiments performed with [125I]UII showed the presence of very-high- and high-affinity binding sites for UII, and a single high-affinity site for URP. Both UII and URP provoked a membrane depolarization accompanied by a decrease in input resistance, stimulated the release of endozepines, neuropeptides specifically produced by astroglial cells, and generated an increase in [Ca2+]c (cytosolic Ca2+ concentration). The UII/URP-induced [Ca2+]c elevation was PTX (pertussis toxin)-insensitive, and was blocked by the PLC (phospholipase C) inhibitor U73122 or the InsP3 channel blocker 2-APB (2-aminoethoxydiphenylborane). The addition of the Ca2+ chelator EGTA reduced the peak and abolished the plateau phase, whereas the T-type Ca2+ channel blocker mibefradil totally inhibited the Ca2+ response evoked by both peptides. However, URP and UII induced a mono- and bi-phasic dose-dependent increase in [Ca2+]c and provoked short- and long-lasting Ca2+ mobilization respectively. Similar mono- and bi-phasic dose-dependent increases in [3H]inositol incorporation into polyphosphoinositides in astrocytes was obtained, but the effect of UII was significantly reduced by PTX, although BRET (bioluminescence resonance energy transfer) experiments revealed that both UII and URP recruited Galphao-protein. Finally, UII, but not URP, exerted a dose-dependent mitogenic activity on astrocytes. Therefore we described that URP and UII exert not only similar, but also divergent actions on astrocyte activity, with UII exhibiting a broader range of activities at physiological peptide concentrations.
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