Article date: June 2005
By: Kaori Mizota, Akira Yoshida, Hitoshi Uchida, Ryousuke Fujita, Hiroshi Ueda in Volume 145, Issue 4, pages 545-550
Agonistic neurosteroids, including pregnenolone, dehydroepiandrosterone and its sulfate (DHEAS), caused rapid degranulation in measurements of β‐hexosaminidase (β‐HEX) release from a mast cell line, RBL‐2H3. This degranulation was blocked by BSA‐conjugated progesterone (PROG‐BSA) or 17β‐estradiol, both of which are antagonistic neurosteroids.
DHEAS‐induced β‐HEX release was blocked by U‐73122 or xestospongin C, but not by PTX or EGTA. DHEAS‐induced β‐HEX release was also abolished by Gq/11‐AS, but not by Gq/11‐MS. Pharmacological analyses revealed that the neurosteroids stimulated a putative membrane receptor through activation of the novel Gq/11 and phospholipase C.
While representative endocrine‐disrupting chemicals (EDCs) did not show any degranulation or nocifensive actions by themselves, they blocked the DHEAS‐induced degranulation.
The binding of a PROG‐BSA‐fluorescein isothiocyanate conjugate (PROG‐BSA‐FITC) to cells was inhibited by neurosteroids and EDCs.
In the algogenic‐induced biting and licking responses test, DHEAS caused agonistic nocifensive actions in a dose‐dependent manner between 1 and 10 fmol (i.pl.). DHEAS‐induced nocifensive actions were abolished by PROG‐BSA or nonylphenol.
Taken together, these results suggest that a Gq/11‐coupled neurosteroid receptor may regulate the neuroimmunological activity related to sensory stimulation and that some EDCs have antagonistic actions for this receptor.
Agonistic neurosteroids, including pregnenolone, dehydroepiandrosterone and its sulfate (DHEAS), caused rapid degranulation in measurements of β‐hexosaminidase (β‐HEX) release from a mast cell line, RBL‐2H3. This degranulation was blocked by BSA‐conjugated progesterone (PROG‐BSA) or 17β‐estradiol, both of which are antagonistic neurosteroids.
DHEAS‐induced β‐HEX release was blocked by U‐73122 or xestospongin C, but not by PTX or EGTA. DHEAS‐induced β‐HEX release was also abolished by Gq/11‐AS, but not by Gq/11‐MS. Pharmacological analyses revealed that the neurosteroids stimulated a putative membrane receptor through activation of the novel Gq/11 and phospholipase C.
While representative endocrine‐disrupting chemicals (EDCs) did not show any degranulation or nocifensive actions by themselves, they blocked the DHEAS‐induced degranulation.
The binding of a PROG‐BSA‐fluorescein isothiocyanate conjugate (PROG‐BSA‐FITC) to cells was inhibited by neurosteroids and EDCs.
In the algogenic‐induced biting and licking responses test, DHEAS caused agonistic nocifensive actions in a dose‐dependent manner between 1 and 10 fmol (i.pl.). DHEAS‐induced nocifensive actions were abolished by PROG‐BSA or nonylphenol.
Taken together, these results suggest that a Gq/11‐coupled neurosteroid receptor may regulate the neuroimmunological activity related to sensory stimulation and that some EDCs have antagonistic actions for this receptor.
British Journal of Pharmacology (2005) 145, 545–550. doi:10.1038/sj.bjp.0706213
DOI: 10.1038/sj.bjp.0706213
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