Publication

CALCINEURIN INHIBITS DESENSITIZATION OF CLONED RAT 5-HT(1C)RECEPTORS

BODDEKE, HWGM., HOFFMAN, BJ., PALACIOS, JM. & HOYER, D., Sep-1993, In : Naunyn-Schmiedebergs Archives of Pharmacology. 348, 3, p. 221-224 4 p.

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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.

Original languageEnglish
Pages (from-to)221-224
Number of pages4
JournalNaunyn-Schmiedebergs Archives of Pharmacology
Volume348
Issue number3
Publication statusPublished - Sep-1993

    Keywords

  • RAT 5-HT(1C)RECEPTORS, A9-CELLS, DESENSITIZATION, CALCINEURIN, PROTEIN-KINASE-C, XENOPUS OOCYTES, RECEPTORS, RESPONSES, BRAIN, BETA

ID: 14146121