Angiotensin II AT(1) and AT(2) receptors contribute to maintain basal adrenomedullary norepinephrine synthesis and tyrosine hydroxylase transcription.
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.
Jezova
Miroslava
M
Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. armandoi@intra.nimh.nih.gov
Armando
Ines
I
Bregonzio
Claudia
C
Yu
Zu-Xi
ZX
Qian
Sujuan
S
Ferrans
Victor J
VJ
Imboden
Hans
H
Saavedra
Juan M
JM
D000313:Adrenal Medulla / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D019439:Chromaffin Cells / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005724:Ganglia / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014157:Transcription Factors; D000804:Angiotensin II; C073402:PD 123319; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine; D004837:Epinephrine