Inactivation of pertussis toxin-sensitive guanyl nucleotide-binding proteins increase parathyroid hormone receptors and reverse agonist-induced receptor down-regulation in ROS 17/2.8 cells.

Endocrinology
A B Abou-SamraG V Segre

Abstract

We examined mechanisms of down-regulation of PTH receptors and desensitization of the PTH-stimulated increase in intracellular cAMP in clonal rat osteosarcoma cells, ROS 17/2.8. ROS cells treated with 10 nM [Nle8,Nle18,Tyr34] bovine (b) PTH-(1-34) amide (NlePTH) for 3 days showed loss of specific PTH binding and PTH-stimulated cAMP accumulation to 10% of that in vehicle-treated control cells. Treatment of these cells with both 0.5 mM 8-bromo-cAMP (8-Br-cAMP) and 1 mM methylisobutylxanthine or 100 ng/ml cholera toxin for 3 days elicited no change in either of these responses. Treatment with 10 nM NlePTH for 3 days did not modify the cAMP accumulation stimulated by 30 microM forskolin or 1 micrograms/ml cholera toxin, indicating that agonist-specific desensitization of PTH-stimulated cAMP accumulation is not due to diminished activity of either the stimulatory guanyl nucleotide regulatory subunit (Gs) or the catalytic subunit of the adenylate cyclase. Treatment of ROS cells with pertussis toxin (PT; 10 ng/ml) for 12, 24, 48, and 72 h increased specific PTH binding by 21%, 28%, 35%, and 39%. The increase in PTH binding was associated with a parallel increase in PTH-stimulated cAMP accumulation and was due to an increase in the num...Continue Reading

Citations

Jun 1, 1994·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·S K Lee, P H Stern
Sep 1, 1996·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J W JongenM P Herrmann-Erlee
Jan 1, 1996·Baillière's Clinical Endocrinology and Metabolism·E M BrownS R Goldring
Dec 11, 1992·Clinical Endocrinology·P P SchachterG S Leight
Mar 15, 2012·American Journal of Physiology. Endocrinology and Metabolism·Hesham A Tawfeek, Abdul B Abou-Samra
Aug 1, 1997·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J A Cole
Jun 17, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D LajeunesseS E Guggino
Oct 12, 2010·The Journal of Endocrinology·Nabanita S DattaAbdul B Abou-Samra
Mar 22, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T MassfelderJ J Helwig
Aug 14, 2001·American Journal of Physiology. Endocrinology and Metabolism·H A TawfeekA B Abou-Samra

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