Calcineurin inhibits desensitization of cloned rat 5-HT(1C) receptorsBoddeke, H. W. G. M., Hoffman, B. J., Palacios, J. M. & Hoyer, D., 11-Nov-1993, In : Naunyn-Schmiedeberg's Archives of Pharmacology. 348, 3, p. 221-224 4 p.
Research output: Contribution to journal › Article › Academic › peer-review
Functional responses to stimulation of rat 5-HT(1C) receptors expressed in A9 cells were studied using whole cell voltage clamp recording technique. Stimulation of 5-HT(1C) receptors with serotonin (5-HT) evoked calcium-dependent outward currents of 109 pA in cells clamped at -50 mV. Pretreatment with the protein kinase C (PKC) activator phorbol myristic acetate (PMA) reduced the 5-HT-induced current amplitude by 46% of the control value. Inclusion of inositol triphosphate (IP3) in the pipette solution induced an outward current of 84 pA. The IP3-induced response was not affected by 60 min pretreatment with PMA. In the presence of the PKC antagonist calphostin C, 60 min treatment with PMA (10-6mol/l) reduced the 5-HT response only by 8%. In cells preincubated with PMA, injection of the calcium/calmodulin dependent serine protein phosphatase calcineurin gradually increased the 5-HT-induced responses by 34%. In A9 cells which were incubated 24 h with the 5-HT(1C) receptor agonist meta chlorophenyl-piperazine hydrochloride (mCPP), 5-HT-induced responses were reduced by 23% of the vehicle pretreated control value. Injection of calcineurin in mCPP treated cells enhanced the 5-HT-induced response by 24%. The results suggest that in A9 cells rat 5-HT(1C) receptors are desensitized after phosphorylation by PKC. This desensitization can be counteracted by calcineurin-induced dephosphorylation.
|Number of pages||4|
|Journal||Naunyn-Schmiedeberg's Archives of Pharmacology|
|Publication status||Published - 11-Nov-1993|
- A9 cells, calcineurin, desensitization, rat 5-HT(1C) receptors, (3 chlorophenyl)piperazine, calphostin C, inositol trisphosphate, phorbol 13 acetate 12 myristate, serotonin, serotonin 2C receptor, animal cell, article, cell line, controlled study, dose time effect relation, fibroblast, genetic transfection, ion current, molecular cloning, mouse, nonhuman, phosphorylation, priority journal, voltage clamp technique