-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells

The pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity has not been elucidated, but apoptosis is thought to play an important role in CsA induced tubular atrophy. Recently Fas-Fas ligand system mediated apoptosis has been frequently reported in many epithelial cells as well as in T lymphocytes. We investigated the ability of CsA to induce apoptosis in cultured human proximal tubular epithelial cells and also the effect of -MSH on them. Fas, Fas ligand, and an intracellular adaptor protein, Fas-associating protein with death domain (FADD) expression, and poly-ADP ribose polymerase (PARP) cleavage were also studied. CsA induced apoptosis in cultured tubular epithelial cells demonstrated by increased number of TUNEL positive cells and it was accompanied by a significant increase in Fas mRNA and Fas ligand protein expressions. FADD and the cleavage product of PARP also increased, indicating the activation of caspase. In -MSH co-treated cells, apoptosis markedly decreased with downregulation of Fas, Fas ligand and FADD expressions and also the cleavage product of PARP. In conclusion, these data suggest that tubular cell apoptosis mediated by Fas system may play a role in tubular atrophy in chronic CsA nephrotoxicity and pretreatment of -MSH may have a some inhibitory effect on CsA induced tubular cell apoptosis.

Topical application of a melanotropin analogue to vulgar vitiligo dermo-epidermal minigrafts

Human subjects with active vulgar vitiligo do not respond well to autologous dermo-epidermal minigrafting. Eighteen subjects were treated with the a-melanocyte-stimulating hormone (a-MSH) synthetic analogue [Nle4, D-Phe7]-a-MSH. The hormone (50 µl, 0.4 mM) was applied topically to 30-cm2 lesions in which 29-48 minigrafts had been made. The hormone did not improve the success of the minigrafting and no differences were observed in local or distant repigmentation in treated subjects as compared to the placebo group. Aliquots of 24-h urine concentrated by lyophilization irreversibly darkened toad skins, demonstrating the presence of the analogue. This is the first report of the transdermal delivery of a topically applied melanotropin in living human subjects

Effects of alpha-MSH and cholinergic agents on cGMP and IP3 levels in rat brain slices

On one hand, it has been demonstrated that the exposure of rat brain slices containing caudate putamen and accumbens nuclei to alpha-MSH brings about an increase in cAMP. This increase is affected when dopamine is present in the incubation medium. On the other hand, an interaction of melanotropinergic-like peptides with acetylcholinergic drugs has been showed to be similar to the one observed with dopamine. In this study we have intended to measure cGMP Or IP3 in response to alpha-MSH, and also to study the interaction with cholinergic drugs by measuring the second messengers recently mentioned. cGMP and IP3 have been measured in tissues and medium in their response to the effect of alpha-MSH alone or in the presence of the peptide plus pilocarpine (selective muscarinic agonist) or atropine (selective muscarinic antagonist). None of them modified the cGMP levels when compared with lhe control group. The exposure of rat brain slices containing CP and Acc nuclei to alpha-MSH resulted in an increase in IP3 levels. Pilocarpine by itself brought about an increase of IP3 only when the highest doses was used. Atropine did not modify the IP3 content. However, when slices were exposured to both alpha-MSH and pilocarpine, IP3 content was similar to control values. The blockage of the muscarinic receptor with atropine blocked the IP3 increase induced by alpha-MSH as well. Therefore, we assume that alpha-MSH does not induce changes in cGMP but it does change the IP3 levels, probably acting at the muscarinic receptor level.

Possible mechanism by which alfa-melanotropin advances the time of vaginal opening

En publicaciones previas se ha comprobado que la administración aguda del péptido alfa-melanotrofina (alfa-MSH) en el día 28 posnatal (PN), a ratas pretratadas con dosis bajas de benzoato de estradiol (BE), induce a un adelanto significativo en el tiempo de aperturas vaginal (AV). Este evento indica la aprición de la pubertad. En cambio, el bloqueo con un anticuerpo específico, del pico sérico de alfa-MSH que se produce normalmente en el día 30PN, retrasa significativamente la AV. En este trabajo de investigación se propuso determinar el rol desempeñado por alfa-MSH en la cadena de eventos neuroendócrínos que conducen a la pubertad. Con el objeto de establecer si el efecto de alfa-MSH sobre la AV, se produce por modificaciones de los patrones de liberación de LH, somatomamotrofinas y/o hormonas esteroides (estradiol, progesterona y testosterona); se sometió a ratas de 28 días de edad, pretratadas con BE, a la administración aguda de alfa-MSH (grupo problema) o con solución salina (SS) (grupo control). En el día 32 PN, los animales se sacrificaron a intervalos horarios entre las 12 y 18 horas. La administración aguda de alfa-MSH incrementó significativamente los niveles de LH, respecto al grupo control. Las otras hormonas estudiadas no experimentaron variaciones significativas por el tratamiento con el péptido. A fin de obtener con mayor exactitud los perfiles de LH desde el día siguiente a la administración de alfa-MSH (29PN) hasta la AV (33PN), se aplicó el tratamiento agudo a animales canulados en la vena yugular externa. Estos se sangraron cada 20 minutos entre las 14:00 y 18 horas. La administración del péptido no modificó significativamente los niveles plasmáticos de LH durante los días 29 y 30 PN. En el grupo tratado con alfa-MSH se produce un incremento en sus niveles en el día 31 PN (adoptando un episodio secretor característico (minisurge), respecto al grupo control. En el día 32 PN,los animales problemas presentan un incremento muy significativo de LH, el cual se produce en el grupo control durante el día 33 PN. Estos resultados nos permitirían proponer que alfa-MSH participaría del complejo sistema de péptidos neuroexcitatorios regulando el comienzo de la pubertad

Alfa-melanotropin induced excessive grooning involve brain acetylcholine possible interaction in the ventral tegmental area

Cuando alfa-MSH es inyectado en el área tegmental ventral (VTA) o intracerebroventricularmente (icv) induce comportamiento de aseo excesivo. La infusión icv del péptido tamién provoca el síndrome de estiramiento y bostezo (SEB). Estos efectos son suprimidos por la administración de atropina intraperitoneal, icv o en el ATV. Las evidencias experimentales presentadas sugerían que alfa-MSH actuaría específicamente sobre una aferencia colinérgica en el ATV. Los resultados indicarían que el péptido actuaría en un blanco neural distinto al sistema dopaminérgico , y originaría los cambios comportamentales recientemente mencionados