AUTORADIOGRAPHIC LOCALIZATION OF [<sup>125</sup>I]–ANGIOTENSIN II BINDING SITES IN THE RAT ADRENAL GLAND

Healy, Dennis P.; Maciejewski, Andrzej R.; Printz, Morton P.

doi:10.1210/endo-116-3-1221

Cited by 36 publications

(11 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the site of synthesis might be different from rat, since by immunocytochemistry, most of the renin-like immunoreactivity in mouse adrenal has been reported to be in the inner cortical region (16). It is of interest to note that in the rat adrenal, renin, converting enzyme activity (28), angiotensin II (15), and angiotensin II receptors (29) (31), and this enzyme may be involved in the processing of prorenin into renin (32).…”

Section: Discussionmentioning

confidence: 99%

Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

Deschepper¹,

Mellon²,

Cumin³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

221

View full text Add to dashboard Cite

Renin gene expression in cells and tissues of the rat was examined by in situ hybridization histochemistry and immunocytochemistry. By using a mouse cDNA probe, hybridization histochemistry revealed renin mRNA in the renal juxtaglomerular cells, testicular Leydig cells, adrenal zona glomerulosa cells, the intermediate lobe of the pituitary, and scattered cells of the anterior lobe of the pituitary. With four separate antisera to mouse submaxillary renin, there was immunoreactivity in the renal juxtaglomerular cells. However, only one of the antisera stained the Leydig cells, a second stained the adrenal zona glomerulosa, a third stained the intermediate lobe of the'pituitary, and a fourth stained scattered cells of the anterior lobe of the pituitary that were identified as gonadotrophs. The variations with the different antisera in detecting extrarenal renin are unexplained but could imply that posttranslational proteolysis or glycosylation of preprorenin varies in different tissues with consequent variations in immunoreactivity. The finding of renin mRNA and renin-like immunoreactivity in these tissues supports the notion that these tissues are sites for production of renin.Renin of renal origin plays an important role in the control of blood pressure by cleaving angiotensinogen into angiotensin I. It is synthesized as a preprorenin that is converted to prorenin and then into active mature renin by proteolytic cleavage (1). In nephrectomized rats, circulating active renin falls to undetectable levels (2), indicating that most or all of the circulating active renin is of renal origin. However, prorenin is still readily detectable and even increases in the plasma of nephrectomized rats (3). These data suggest that some extrarenal tissues also express the renin gene.Studies using renin activity assays of whole tissue extracts have detected renin-like activity in many different extrarenal tissues. These include the submaxillary glands (4), uterus (5, 6), placenta (7), brain (8, 9), anterior pituitary (10), testis (11), and adrenals (12, 13) of rats, rabbits, humans, and other mammalian species. In most ofthese studies, inhibition ofthe renin activity by specific renin antibodies and determination of the pH optimum have separated the renin-like activity from other enzymes that can generate angiotensin. In some instances, immunocytochemistry or enzymatic assays in specific tissue fractions provided information about the localization of renin in the tissue; examples include the rat adrenal glomerulosa (14, 15), the inner cortex of the mouse adrenal (16), the Leydig cells of the rat testes (17, 18), the renal juxtaglomerular cells of rodents (19), and the gonadotrophs of the rat pituitary (20).However, the presence of renin in a tissue does not demonstrate synthesis of the protein in the tissue; a better indication that renin is actually produced is demonstration of its mRNA in the tissue. In mouse kidneys, adrenals, and testes, renin mRNA has been detected by hybridization of total tissue RNA (21). However, th...

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

Deschepper¹,

Mellon²,

Cumin³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

221

View full text Add to dashboard Cite

show abstract

“…Increasing evidence has demonstrated the existence of local extra-circulatory RAS in many tissues, including the brain (Dzau etal., 1986;Ganten etal., 1983;Healey & Printz, 1984;Mendelsohn, 1985). The identification of renin, ACE and angiotensin II receptors in the endothelium of the vascular wall throughout the vasculature, including brain arteries (Dzau, 1984(Dzau, , 1988Ganten et al, 1983;Swales & Thurston, 1973), has stimulated research on the influence of the RAS on regional blood flows.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin converting enzyme inhibition and cerebral circulation‐a review.

Waldemar

Paulson

1989

Brit J Clinical Pharma

View full text Add to dashboard Cite

1. The identification of a vascular wall renin angiotensin system and of angiotensin converting enzyme on the luminal surface of the endothelium in many tissues, including the brain, has stimulated research on the influence of the renin angiotensin system on regional blood flows. 2. In experimental studies inhibition of the angiotensin converting enzyme shifts the limits of cerebral blood flow autoregulation towards lower blood pressure values. 3. In patients with chronic arterial hypertension and in patients with chronic heart failure cerebral blood flow is not changed by acute or chronic angiotensin converting enzyme inhibition, despite in some cases pronounced reductions in the mean arterial blood pressure. Angiotensin converting enzyme inhibition does not change ischaemic regional cerebral blood flow in acute stroke. 4. It is concluded that following angiotensin converting inhibition cerebral blood flow is maintained at an unchanged level. The mechanism may include inhibition of locally produced angiotensin II leading to a selective dilation of larger cerebral arteries with a compensatory constriction of the smaller cerebral arteries.

show abstract

“…After subcloning of corresponding Agtr1a promoter fragments into the promoterless luciferase reporter plasmid pGL3-Basic, the promoter/reporter plasmids were transfected into PC12 pheochromocytoma cells; rodent chromaffin cells were chosen because the angiotensin II (type 1) receptor is highly expressed in such cells (8,17,21).…”

Section: Agtr1a Mrna Abundance: Rt-pcrmentioning

confidence: 99%

“…Since the angiotensin II (type 1) receptor is expressed in the rodent adrenal gland (8), including chromaffin cells (8), where it may regulate catecholamine release (19), we studied the abundance of Agtr1a transcripts in the adrenal glands of the three strains, using RT-PCR (Fig. 4).…”

Section: Background To the Experiments: Blood Pressure Linkage And Thmentioning

confidence: 99%

The angiotensin II receptor (Agtr1a): functional regulatory polymorphisms in a locus genetically linked to blood pressure variation in the mouse

Wong

Mahapatra

Chitbangonsyn

et al. 2003

Physiological Genomics

View full text Add to dashboard Cite

Hypertension is a complex trait with multiple genetic determinants. A previous genome-wide linkage study of systolic blood pressure in a mouse genetic backcross implicated a region of chromosome 13 (LOD = 3.3 at 16.0 cM) as a determinant of blood pressure differences between a hereditary low blood pressure strain of Mus musculus (BPL/1) and Mus spretus (SPRET); at this locus, the unexpected effect of the BPL/1 allele was to increase blood pressure. A plausible candidate locus encoding angiotensin II receptor isoform 1a (Agtr1a) is also located at 16.0 cM on chromosome 13. We therefore investigated structural and functional differences at Agtr1a between BPL/1 and SPRET, as well as the BPH/2 strain. Resequencing Agtr1a in the three strains established the exon/intron and proximal promoter structure of the mouse gene. Coding exon 3 spanned 1,960 bp (with 26 SNPs), including the 1,077-bp/359-amino acid ORF (with 5 cSNPs, all of which were synonymous). Promoter sequences revealed a consensus TATA box, conserved G/C-rich regions, and a striking, lengthy simple sequence repeat region, composed of di-, tri-, tetra-, and penta-nucleotide repeats, whose overall length varied markedly among the strains. Twenty-five other SNPs and three single nucleotide deletions differentiated the strains’ promoters, six of which were in likely functional promoter motifs. Agtr1a mRNA abundance in the adrenal gland in vivo was greater ( P < 0.05) in BPL/1 than SPRET, consistent with the predicted effect of the BPL/1 allele to confer higher blood pressure. When Agtr1a promoters were subcloned into luciferase reporter plasmids and transfected into PC12 chromaffin cells, basal promoter expression was higher ( P < 0.001) in BPL/1 than in SPRET, consistent with the endogenous mRNA results. In summary, Agtr1a on chromosome 13 is highly polymorphic between mouse strains, although the amino acid sequence specified by the ORF is invariant, even across mouse species. We conclude that polymorphisms in the Agtr1a promoter account for differences in gene expression in vivo between BPL/1 and SPRET, in a way consistent with the effects of alleles at this locus on chromosome 13 to affect blood pressure in the mouse genome-wide linkage study.

show abstract

AUTORADIOGRAPHIC LOCALIZATION OF [¹²⁵I]–ANGIOTENSIN II BINDING SITES IN THE RAT ADRENAL GLAND

Cited by 36 publications

References 7 publications

Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

Angiotensin converting enzyme inhibition and cerebral circulation‐a review.

The angiotensin II receptor (Agtr1a): functional regulatory polymorphisms in a locus genetically linked to blood pressure variation in the mouse

Contact Info

Product

Resources

About

AUTORADIOGRAPHIC LOCALIZATION OF [125I]–ANGIOTENSIN II BINDING SITES IN THE RAT ADRENAL GLAND

Cited by 36 publications

References 7 publications

Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

Angiotensin converting enzyme inhibition and cerebral circulation‐a review.

The angiotensin II receptor (Agtr1a): functional regulatory polymorphisms in a locus genetically linked to blood pressure variation in the mouse

Contact Info

Product

Resources

About

AUTORADIOGRAPHIC LOCALIZATION OF [¹²⁵I]–ANGIOTENSIN II BINDING SITES IN THE RAT ADRENAL GLAND