Biologia, Bratislava 55/3: 299-303, 2000.

ISSN 0006-3088 (Biologia). ISSN 1335-6399 (Biologia. Section Cellular and Molecular Biology).

 

Full Paper

Counteractive b-adrenergic and endothelin subtype-ETB receptor signalling modulate proliferation in monkey renal cells (MRC).

 

Jan Drimal1*, Katarina Bauerova1, Vladimir Knezl1 & Viktor Kettmann2

1 Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dubravska 9, SK-84216 Bratislava, Slovakia; tel.: ++421 7 59410660, fax: ++421 7 54775928, e-mail: exfadrim@savba.sk

2 Department of Analytical Chemistry, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia

* corresponding author

Received: October 21, 1999 / Accepted: February 16, 2000

 

Abstract

The purpose of this study was to establish whether cross-regulatory signalling from membrane- bound b-adrenergic and endothelin receptors may modulate specific subtype-ETB receptor down-regulation and proliferation in cultured MRC. To determine whether these changes could lead to ETB receptor down-regulation, isoproterenol (IPN), immobilized IPN-copolymer (IPN-CP), photolabile, caged cyclic nucleotides (Caged-cAMP and Caged-cGMP) and two endothelin agonists (ET-1 and synthetic, truncated (8-21)ET-1 derivative) were used in the present study to stimulate cells. The ETB selective ligand [125I]IRL-1620 in equilibrium-binding, [3H]thymidine in incorporation experiments, cyclic nucleotides (cAMP and cGMP) and endothelin RIA assays in MRC were used to characterize the major component of -adrenergic and endothelin signalling, sub-type ETB receptor regulation and proliferation response. The results obtained in this study document β-adrenergic, cyclic AMP mediated inhibition of proliferation and ETB selective down-regulation of surface-membrane endothelin receptors in stimulated cells.

 

Key words: endothelin-1, ETB receptors, down-regulation, proliferation, cyclic nucleotides, monkey renal cells.