Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells.
Physiol Genomics
; 5(1): 11-9, 2001 Feb 07.
Article
en En
| MEDLINE
| ID: mdl-11161002
ABSTRACT
Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either alpha-melanocyte-stimulating hormone (alpha-MSH) or desacetyl-alpha-MSH, mediate increases in intracellular free calcium concentration ([Ca(2+)](i)) with EC(50) values between 0.3 and 4.3 nM. The increase in [Ca(2+)](i) is cholera toxin sensitive and pertussis toxin insensitive. The mechanism involves calcium mobilization from intracellular stores without a transient rise in inositol trisphosphate. Mouse agouti protein (55 nM) is a competitive antagonist of alpha-MSH (6-fold) and desacetyl-alpha-MSH (8-fold), coupling the mMC1-R to increased [Ca(2+)](i). Agouti protein (55 nM) significantly increased the EC(50) for alpha-MSH (3-fold), and 550 nM agouti protein significantly increased the EC(50) for desacetyl-alpha-MSH (4-fold), coupling the mMC4-R to a rise in [Ca(2+)](i). However, agouti protein antagonism of the MC4-R may not be competitive since there was a trend for the maximum response to also increase. There was no significant antagonism of the MC3-R and MC5-R by agouti protein (55 nM). Understanding the physiological relevance of the transduction of a calcium signal by melanocortin peptides may be important for future development of therapeutic targeting of the melanocortin receptors.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_cholera
Asunto principal:
Alfa-MSH
/
Calcio
/
Receptores de Corticotropina
/
Péptidos y Proteínas de Señalización Intercelular
/
Receptor de Melanocortina Tipo 3
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Physiol Genomics
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2001
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda