Key result
Long-term AT1 and AT2 receptor blockade decreased adrenomedullary norepinephrine content and tyrosine hydroxylase transcription, indicating both receptors regulate basal norepinephrine formation.
Both AT1 and AT2 receptors play a role in the selective regulation of basal norepinephrine formation and tyrosine hydroxylase transcription in the adrenal medulla, involving common and distinct regulatory mechanisms.
AT1-AT2 receptor interactions in adrenal medulla merit further study; leaves open any impact on clinical ARB use.
Angiotensin II (Ang II) AT(1) receptors have been proposed to mediate the Ang II-dependent and the stress-stimulated adrenomedullary catecholamine synthesis and release. However, in this tissue, most of the Ang II receptors are of the AT(2) type. We asked the question whether AT(1) and AT(2) receptors regulate basal catecholamine synthesis. Long-term AT(1) receptor blockade decreased adrenomedullary AT(1) receptor binding, AT(2) receptor binding and AT(2) receptor protein, rat tyrosine hydroxylase (TH) mRNA, norepinephrine (NE) content, Fos-related antigen 2 (Fra-2) protein, phosphorylated cAMP response element binding protein (pCREB), and ERK2. Long-term AT(2) receptor blockade decreased AT(2) receptor binding, TH mRNA, NE content and Fra-2 protein, although not affecting AT(1) receptor binding or receptor protein, pCREB or ERK2. Angiotensin II colocalized with AT(1) and AT(2) receptors in ganglion cell bodies. AT(2) receptors were clearly localized to many, but not all, chromaffin cells. Our data support the hypothesis of an AT(1)/AT(2) receptor cross-talk in the adrenomedullary ganglion cells, and a role for both receptor types on the selective regulation of basal NE, but not epinephrine formation, and in the regulation of basal TH transcription. Whereas AT(1) and AT(2) receptors involve the Fos-related antigen Fra-2, AT(1) receptor transcriptional effects include pCREB and ERK2, indicating common as well as different regulatory mechanisms for each receptor type.
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Ježová et al. (2003) studied Basal adrenomedullary norepinephrine synthesis. AT1 and AT2 receptor blockade was evaluated on Adrenomedullary norepinephrine synthesis and tyrosine hydroxylase transcription. Long-term AT1 and AT2 receptor blockade decreased adrenomedullary norepinephrine content and tyrosine hydroxylase transcription, indicating both receptors regulate basal norepinephrine formation.
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