Characterization of acute homologous desensitization of μ-opioid receptor-induced currents in locus coeruleus neurones
Article first published online: 19 JUL 2012
1995 British Pharmacological Society
British Journal of Pharmacology
Volume 115, Issue 6, pages 925–932, July 1995
How to Cite
Osborne, P.B. and Williams, J.T. (1995), Characterization of acute homologous desensitization of μ-opioid receptor-induced currents in locus coeruleus neurones. British Journal of Pharmacology, 115: 925–932. doi: 10.1111/j.1476-5381.1995.tb15899.x
- Issue published online: 19 JUL 2012
- Article first published online: 19 JUL 2012
- Received January 20, 1995; Revised March 20, 1995; Accepted March 30, 1995
- Locus coeruleus;
- phosphoprotein phosphatase;
- drug tolerance
- 1Acute homologous desensitization of μ-opioid receptor-induced currents was pharmacologically characterized in locus coeruleus (LC) neurones by use of intracellular and whole cell recording in superfuised brain slices.
- 2Following desensitization of opioid receptors by perfusion with a high concentration of [Met5] enkephalin (ME) for 5 min, there was a reduction in the maximum response and a rightward shift of the concentration - response curves for ME, [D-Ala2, N-MePhe4, Gly - ol] enkephalin (DAMGO) and nor-morphine.
- 3By simultaneously fitting the operational model to the paired pre- and post-desensitization concentration-response data for each agonist, estimates of the level of desensitization were obtained. The values obtained for the three agonists (between 88% and 96%) were similar and did not vary according to the efficacy of the agonist used.
- 4Use of whole cell patch recording techniques caused a slow rundown in the amplitude of ME currents (approx. 40% reduction over 60 min) but did not greatly affect the expression of acute desensitization of opioid currents.
- 5When included in the patch recording solution, the phosphatase inhibitors, microcystin (50 nM-4 μm) and okadaic acid (1 μm) had no effect on the induction of desensitization or the normal ability of opioid or α2-adrenoceptors to produce currents. Microcystin decreased the rate of recovery of the ME (300 nM) currents following desensitization; however, okadaic acid had little effect on the rate of recovery from desensitization.
- 6Strong calcium buffering with BAPTA (10–20 mM) had no effect on desensitization or the recovery from desensitization.
- 7These results suggest that acute homologous desensitization of μ-opioid receptors in LC neurones entails a rapid loss of responsiveness that involves a majority of the receptor population. The mechanism by which desensitization is reversed may involve a non-calcium-dependent protein phosphatase but the processess that cause desensitization remain unclear.