Original Paper

Neurochemical Research

, Volume 34, Issue 5, pp 953-963

First online:

Short-term Effects of Endothelins on Tyrosine Hydroxylase Activity and Expression in the Olfactory Bulb of Normotensive Rats

  • Sabrina L. NabhenAffiliated withCátedra de Fisiología, Instituto de Química y Metabolismo del Fármaco-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
  • , Guadalupe PerfumeAffiliated withCátedra de Fisiología, Instituto de Química y Metabolismo del Fármaco-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
  • , María A. BattistoneAffiliated withCátedra de Fisiología, Instituto de Química y Metabolismo del Fármaco-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
  • , Andrés RossiAffiliated withCátedra de Fisiología, Instituto de Química y Metabolismo del Fármaco-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
  • , Tamara AbramoffAffiliated withCátedra de Fisiología, Instituto de Química y Metabolismo del Fármaco-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
  • , Liliana G. BianciottiAffiliated withCátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
  • , Marcelo S. VattaAffiliated withCátedra de Fisiología, Instituto de Química y Metabolismo del Fármaco-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IQUIMEFA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires Email author 

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Abstract

The olfactory system in rats is part of the limbic region with extensive afferent connections with brain areas involved in the regulation of behaviour and autonomic responses. The existence of the endothelin system and catecholaminergic neurons in the olfactory bulb suggests that endothelins may modulate noradrenergic transmission and diverse olfactory mediated processes. In the present work we studied the effect of endothelin-1 and -3 on neuronal norepinephrine release and the short-term regulation of tyrosine hydroxylase in the olfactory bulb. Results showed that both endothelins increased tyrosine hydroxylase activity through the activation of a non-conventional endothelin G-protein coupled receptor, coupled to the stimulation of protein kinase A and C, as well as Ca2+/calmodulin-dependent protein kinase II. On the other hand, neither endothelin-1 nor endothelin-3 modified tyrosine hydroxylase total protein levels, but both peptides increased the phosphorylation of serine residues of the enzyme at sites 19 and 40. Furthermore, endothelins enhanced norepinephrine release in olfactory neurons suggesting that this event may contribute to increased tyrosine hydroxylase activity by reducing the feedback inhibition. Taken together present findings show a clear interaction between the endothelin system, and the catecholaminergic transmission in the olfactory bulb. Additional studies are required to evaluate the physiological functions regulated by endothelins at this brain level.

Keywords

Endothelin-1 Endothelin-3 Norepinephrine release Olfactory bulb Tyrosine hydroxylase activity Tyrosine hydroxylase expression