cAMP-dependent down-regulation of endothelin-1 receptors on rat astrocytoma C6 cells.
The density of endothelin-1 (ET-1) receptors on rat astrocytoma C6 cells is down-regulated by activation of protein kinase C (PKC). We have investigated whether intracellular accumulation of cyclic adenosine monophosphate (cAMP) may also modulate surface ET-1 receptor number. The density of ET-1 receptors was measured by binding of [125I]ET-1 on rat astrocytoma C6 intact cells exposed to catecholamines, dibutyryl-cAMP or forskolin. Prolonged exposure of the cells to the beta-adrenergic agonists, isoproterenol or noradrenaline, results in a time- and dose-dependent decrease in cell surface ET-1 receptor number. This decrease proceeds slowly: maximal down-regulation is obtained by 6-7 h and sustained for up to 24 h in the presence of 10 microM isoproterenol. Since this down-regulation is mimicked by dibutyryl-cAMP (4 microM) and by forskolin (10 microM), we conclude that ET-1 receptors are susceptible to down-regulation through a cAMP-dependent pathway.
Durieu-Trautmann
O
O
Laboratoire d'Immuno-Pharmacologie Moléculaire, CNRS UPR 0415, Université Paris VII, France.
Couraud
P O
PO
Foignant-Chaverot
N
N
Strosberg
A D
AD
D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D016232:Endothelins / Q000502:physiology*; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D017466:Receptors, Endothelin
D016232:Endothelins; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D011493:Protein Kinase C; D007545:Isoproterenol; D009638:Norepinephrine