Involvement of protein kinase C in the first step of vasopressin sensitive phospholipase C homologous desensitization

Anne Louise Savage, Francis Daro, Gilles Gullion

Research output: Contribution to journalArticle

Abstract

In WRK1 cells, a rat mammary tumor cell line, arginine vasopressin (AVP) stimulates phosphoinositide (PI) turnover and calcium mobilization. We wxamined the influence of phorbol ester PDBu (a protein kinase C activator) on the AVP-sensitive accumulation of inositol phosphate and thus studied the possible involvement of protein kinase C in the homologous mechanisms of desensitization of vasopressin receptor.
PDBu was shown to inhibit vasopressin-stimulated inositol phosphate accumulation in a dosedependent manner (ED50 around 5nM). High pressure liquid chromatography (HPLC) experiments demonstrated that Ins1P, Ins(1,4)P2, Ins(1,3,4)P3 and Ins(1,4,5)P3 accumulations were reduced. This inhibiroty effect was specific to active phorbol esters like PDBu, since it was not observed with the inactive phorbol ester 4 αPDD. For short period of incubation, PDBu had no effect on the specific binding of [3H]-AVP to its specific receptors and weakly inhibited basal and sodium fluoride-stimulated phospholipase C activities.These results wuggest that protein kinase C activation may alter the coupling between the vasopressin receptor and the G protein which coulpled the hormonal receptor to the phospholipase C. Such mechanisms were probably involved in the homologous desensitization of vasopressin receptor, since staurosporine (a PKC inhibitor) both reversed PDBu inhibitory effects and the first step of vasopressin homologous desensitization.
Original languageEnglish
Pages (from-to)121-138
Number of pages18
JournalBiochemistry. Life Sciences Advances
Publication statusPublished - 1993
Externally publishedYes

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Vasopressin Receptors
Arginine Vasopressin
Type C Phospholipases
Phorbol Esters
Vasopressins
Protein Kinase C
Inositol Phosphates
Sodium Fluoride
Staurosporine
Phosphatidylinositols
Tumor Cell Line
GTP-Binding Proteins
High Pressure Liquid Chromatography
Breast Neoplasms
Calcium

Cite this

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title = "Involvement of protein kinase C in the first step of vasopressin sensitive phospholipase C homologous desensitization",
abstract = "In WRK1 cells, a rat mammary tumor cell line, arginine vasopressin (AVP) stimulates phosphoinositide (PI) turnover and calcium mobilization. We wxamined the influence of phorbol ester PDBu (a protein kinase C activator) on the AVP-sensitive accumulation of inositol phosphate and thus studied the possible involvement of protein kinase C in the homologous mechanisms of desensitization of vasopressin receptor.PDBu was shown to inhibit vasopressin-stimulated inositol phosphate accumulation in a dosedependent manner (ED50 around 5nM). High pressure liquid chromatography (HPLC) experiments demonstrated that Ins1P, Ins(1,4)P2, Ins(1,3,4)P3 and Ins(1,4,5)P3 accumulations were reduced. This inhibiroty effect was specific to active phorbol esters like PDBu, since it was not observed with the inactive phorbol ester 4 αPDD. For short period of incubation, PDBu had no effect on the specific binding of [3H]-AVP to its specific receptors and weakly inhibited basal and sodium fluoride-stimulated phospholipase C activities.These results wuggest that protein kinase C activation may alter the coupling between the vasopressin receptor and the G protein which coulpled the hormonal receptor to the phospholipase C. Such mechanisms were probably involved in the homologous desensitization of vasopressin receptor, since staurosporine (a PKC inhibitor) both reversed PDBu inhibitory effects and the first step of vasopressin homologous desensitization.",
author = "Savage, {Anne Louise} and Francis Daro and Gilles Gullion",
year = "1993",
language = "English",
pages = "121--138",
journal = "Biochemistry. Life Sciences Advances",

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TY - JOUR

T1 - Involvement of protein kinase C in the first step of vasopressin sensitive phospholipase C homologous desensitization

AU - Savage, Anne Louise

AU - Daro, Francis

AU - Gullion, Gilles

PY - 1993

Y1 - 1993

N2 - In WRK1 cells, a rat mammary tumor cell line, arginine vasopressin (AVP) stimulates phosphoinositide (PI) turnover and calcium mobilization. We wxamined the influence of phorbol ester PDBu (a protein kinase C activator) on the AVP-sensitive accumulation of inositol phosphate and thus studied the possible involvement of protein kinase C in the homologous mechanisms of desensitization of vasopressin receptor.PDBu was shown to inhibit vasopressin-stimulated inositol phosphate accumulation in a dosedependent manner (ED50 around 5nM). High pressure liquid chromatography (HPLC) experiments demonstrated that Ins1P, Ins(1,4)P2, Ins(1,3,4)P3 and Ins(1,4,5)P3 accumulations were reduced. This inhibiroty effect was specific to active phorbol esters like PDBu, since it was not observed with the inactive phorbol ester 4 αPDD. For short period of incubation, PDBu had no effect on the specific binding of [3H]-AVP to its specific receptors and weakly inhibited basal and sodium fluoride-stimulated phospholipase C activities.These results wuggest that protein kinase C activation may alter the coupling between the vasopressin receptor and the G protein which coulpled the hormonal receptor to the phospholipase C. Such mechanisms were probably involved in the homologous desensitization of vasopressin receptor, since staurosporine (a PKC inhibitor) both reversed PDBu inhibitory effects and the first step of vasopressin homologous desensitization.

AB - In WRK1 cells, a rat mammary tumor cell line, arginine vasopressin (AVP) stimulates phosphoinositide (PI) turnover and calcium mobilization. We wxamined the influence of phorbol ester PDBu (a protein kinase C activator) on the AVP-sensitive accumulation of inositol phosphate and thus studied the possible involvement of protein kinase C in the homologous mechanisms of desensitization of vasopressin receptor.PDBu was shown to inhibit vasopressin-stimulated inositol phosphate accumulation in a dosedependent manner (ED50 around 5nM). High pressure liquid chromatography (HPLC) experiments demonstrated that Ins1P, Ins(1,4)P2, Ins(1,3,4)P3 and Ins(1,4,5)P3 accumulations were reduced. This inhibiroty effect was specific to active phorbol esters like PDBu, since it was not observed with the inactive phorbol ester 4 αPDD. For short period of incubation, PDBu had no effect on the specific binding of [3H]-AVP to its specific receptors and weakly inhibited basal and sodium fluoride-stimulated phospholipase C activities.These results wuggest that protein kinase C activation may alter the coupling between the vasopressin receptor and the G protein which coulpled the hormonal receptor to the phospholipase C. Such mechanisms were probably involved in the homologous desensitization of vasopressin receptor, since staurosporine (a PKC inhibitor) both reversed PDBu inhibitory effects and the first step of vasopressin homologous desensitization.

M3 - Article

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EP - 138

JO - Biochemistry. Life Sciences Advances

JF - Biochemistry. Life Sciences Advances

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