ISSN:
1432-1912
Keywords:
Rat 5-HT1C receptors
;
A9 cells
;
Desensitization
;
Calcineurin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Functional responses to stimulation of rat 5-HT1C receptors expressed in A9 cells were studied using whole cell voltage clamp recording technique. Stimulation of 5-HT1C 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 (10−6 mol/1) reduced the 5-HT response only by 8%. In cells preincubated with PMA, injection of the calcium/calmodulin dependent serine proteinphosphatase calcineurin gradually increased the 5-HT-induced responses by 34%. In A9 cells which were incubated 24 h with the 5-HT1C receptor agonist meta chlorophenylpiperazine 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-HT1C receptors are desensitized after phosphorylation by PKC. This desensitization can be counteracted by calcineurin-induced: dephosphorylation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169147
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