INVESTIGADORES
VATTA Marcelo Sergio
artículos
Título:
Endothelin-1 and -3 modulate the neuronal norepinephrine transporter through
Autor/es:
HOPE S; NABHEN S; SORIA C; BIANCIOTTI LG; VATTA MS
Revista:
NEUROCHEMISTRY INTERNATIONAL
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2010 vol. 57 p. 306 - 313
ISSN:
0197-0186
Resumen:
We have previously reported that endothelin-1 and -3 modulate different steps of noradrenergic
transmission in the hypothalamus. We showed that endothelins modify neuronal norepinephrine
transport activity through the regulation of the kinetic constant and internalization. In the present work
we sought to define the endothelin receptors and intracellular mechanisms involved in the downregulation
of neuronal norepinephrine uptake induced by endothelin-1 and -3 in the rat posterior
hypothalamic region. Results showed that endothelin-1 reduced norepinephrine uptake through ETBB
receptors, whereas endothelin-3 through a non-conventional or atypical endothelin receptor. In both
cases, the effect on norepinephrine uptake was coupled to protein kinase A and C as well as nitric oxide
pathways. However, neither protein kinase G nor intracellular or extracellular calcium and calcium/
calmodulin-dependent protein kinase II were involved. In addition, the same intracellular mechanisms
participated in the reduction of nisoxetine binding (norepinephrine transporter internalization index)
induced by both endothelins. Present findings reveal the underlying mechanisms involved in the
regulation of the neuronal norepinephrine transporter by endothelins and further support the role of
these peptides in the modulation of noradrenergic transmission at the presynaptic nerve endings in the
posterior hypothalamus.