Characterization of pancreastatin receptor and signaling in rat HTC hepatoma cells.
Eur J Pharmacol
; 397(2-3): 229-35, 2000 Jun 02.
Article
en En
| MEDLINE
| ID: mdl-10844119
ABSTRACT
Pancreastatin, a chromogranin A-derived peptide widely distributed throughout the neuroendocrine system, has a general inhibitory effect on endocrine secretion and a counterregulatory effect on insulin action. We have recently described the cross-talk of pancreastatin with insulin signaling in rat hepatoma cells (HTC), where it inhibits insulin action and signaling through the serine phosphorylation of the insulin receptor, thereby impairing tyrosine kinase activity. Here, we have characterized pancreastatin receptors and signaling in HTC cells. The pancreastatin effector systems were studied by determining phospholipase C activity in HTC membranes and mitogen-activated protein kinase (MAPK) phosphorylation activity in HTC cells. Binding studies with radiolabeled pancreastatin showed a population of high affinity binding sites, with a B(max) of 8 fmol/mg protein and a K(d) of 0.6 nM. Moreover, we assessed the coupling of the receptor with a G protein system by inhibiting the binding with guanine nucleotide and by measuring the GTP binding to HTC membranes. We found that pancreastatin receptor was coupled with a G alpha(q/11) protein which activates phospholipase C-beta(1) and phospholipase C-beta(3), in addition to MAPK via both beta gamma and alpha(q/11).
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Colección:
01-internacional
Asunto principal:
Receptores de la Hormona Gastrointestinal
/
Transducción de Señal
/
Carcinoma Hepatocelular
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2000
Tipo del documento:
Article
País de afiliación:
España