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Regulation of Angiotensin II Type 1 Receptor mRNA in Neuronal Cultures of Normotensive and Spontaneously Hypertensive Rat Brains by Phorbol Esters and Forskolin
Author(s) -
Lu Di,
Sumners Colin,
Raizada Mohan K.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62062079.x
Subject(s) - forskolin , medicine , endocrinology , stimulation , protein kinase c , receptor , biology , phorbol , staurosporine , messenger rna , angiotensin ii , kinase , microbiology and biotechnology , biochemistry , gene
Neuronal cells in primary culture from the brains of normotensive, Wistar‐Kyoto (WKY) rats and spontaneously hypertensive (SH) rats express angiotensin II type 1 (AT 1 ) receptors. Treatment of WKY rat brain cultures with a phorbol ester, phorbol 12‐myristate 13‐acetate (PMA), causes a time‐and dose‐dependent increase in the levels of an ˜2.3‐kb AT 1 receptor mRNA transcript. A maximal stimulation of 4.5‐fold in the AT 1 receptor mRNA transcript level is observed with 200 n M PMA in 4 h and is blocked by 1 μ M staurosporine. Forskolin also increases the AT 1 receptor mRNA levels in WKY rat brain neurons in a time‐and dose‐dependent manner, and a 4.5‐fold stimulation is achieved with 50μ M forskolin in 4 h. The stimulatory effects of both PMA and forskolin are completely abolished by coincubation of neuronal cultures with 1 μ M actinomycin D. In addition, nuclear run‐on assay indicated an increase in the transcription of AT 1 receptor mRNA in WKY rat brain neurons treated with either PMA or forskolin. Both PMA and forskolin also stimulate levels of AT 1 receptor mRNA in neuronal cultures from brain of the SH rat. The degree of stimulation in these cultures is comparable to that in WKY rat brain neurons. These observations show that although the basal AT 1 receptor gene expression is significantly higher in SH rat brain neurons compared with WKY rat brain neurons, the protein kinase C‐and protein kinase A‐responsive stimulation is not altered. These data suggest a possible involvement of protein kinase C and protein kinase A response elements in AT 1 receptor gene expression.