Desensitization of muscarinic receptor-coupled inositol phospholipid hydrolysis in human detrusor cultured smooth muscle cells

Marsh, K. A. and Harriss, D. R. and Hill, S. J. (1996) Desensitization of muscarinic receptor-coupled inositol phospholipid hydrolysis in human detrusor cultured smooth muscle cells. The Journal of Urology, 155 (4). pp. 1439-1443. ISSN 0022-5347

Full content URL: http://dx.doi.org/10.1016/S0022-5347(01)66303-1

Others
S0022534701663031
[img]
[Download]
[img] HTML
S0022534701663031

56kB
Item Type:Article
Item Status:Live Archive

Abstract

PURPOSE: The aim of this study was to investigate the desensitization characteristics of muscarinic M3 receptors in primary cultures of human detrusor smooth muscle cells. MATERIALS AND METHODS: Cell cultures were prepared from cold cup pinch biopsies of the human detrusor muscles by explant culture methods. Accumulation of (3)H-inositol phosphates was measured on confluent monolayers as described previously in detail. Desensitization was achieved by pre-incubating the cells with carbachol or histamine for 5 to 60 minutes. RESULTS: Carbachol induced a concentration-dependent increase in phosphoinositide turnover in naive cells, the response being rapid and evident after only a 30-second exposure to the agonist. Pre-incubation of the cells with carbachol produced a concentration-dependent decrease in the inositol phosphate response to a second challenge with carbachol. Pre-exposure to carbachol for only 5 minutes prior to a re-challenge reduced the mean size of response of the second stimulation to 49% of that observed in naive cells. Pre-exposure of the cells to histamine did not alter the response of the cells to a subsequent challenge with carbachol and vice versa. CONCLUSIONS: The muscarinic receptors retained by human detrusor smooth muscle cells in culture are susceptible to a desensitization of the carbachol-induced increase phosphoinositide turnover observed in these cells. This desensitization is rapid, and the results indicate that it is homologous and does not occur via a postreceptor mechanism but at the level of the receptor itself.

Keywords:Muscarinic, detrusor
Subjects:B Subjects allied to Medicine > B210 Pharmacology
Divisions:College of Science > School of Life Sciences
ID Code:27567
Deposited On:24 May 2017 13:35

Repository Staff Only: item control page