Differential regional expression of three natriuretic peptide receptor genes within primate tissues.

Abstract

The natriuretic peptide receptors are three homologous cell surface proteins, each with a single transmembrane domain. The atrial natriuretic peptide receptor type A (ANPRA) and the homologous receptor type B (ANPRB) are both membrane guanylyl cyclases that synthesize cyclic GMP as an intracellular second messenger. The third receptor in this family, the atrial natriuretic peptide receptor type C (ANPRC), is not coupled to cyclic GMP production. We report on the distribution of the ANPRA, ANPRB, and ANPRC mRNAs in rhesus monkey tissues assayed by in situ hybridization. ANPRA mRNA is most abundantly expressed in the kidney glomerulus, adrenal zona glomerulosa, pituitary, cerebellum, and endocardial endothelial cells of the right and left atrium and right ventricle. In contrast, abundant ANPRB expression appears to be confined to the adrenal medulla, pituitary, and cerebellum. ANPRC mRNA appeared to be expressed very differently than ANPRA and ANPRB. In the heart, ANPRC mRNA is expressed most prominently in endocardial endothelial cells of all four chambers but is also found throughout the myocardium only in the right atrium. These data identify major sites of natriuretic peptide receptor mRNA expression and suggest that there may be prominent cell type-specific differential distribution of these receptors in central and peripheral targets for the natriuretic peptides.Natriuretic peptides are a family of homologous polypeptide hormones that function in both central and peripheral control of fluid volume regulation. As such, these hormones are in dynamic mutual antagonism to the hypertensive renin/angiotensin II/aldosterone system. Of the three known hormones in this family, atrial natriuretic peptide (ANP) (reviewed in reference 13), brain natriuretic peptide (BNP) (37), and type C natriuretic peptide (CNP) (38), ANP has been the most intensely studied, with documented effects on the kidney, adrenals, vasculature, pituitary, and brain. Both ANP and the more recently described BNP are primarily cardiac hormones (26) that are released by the heart in its role as an endocrine organ, regulating fluid and electrolyte homeostasis. A variety of extra-atrial sites of ANP expression have been described (13), suggesting a localized paracrine role for ANP in some tissues. In contrast, the expression of the newly discovered hormone CNP appears to be limited to the nervous system (15).Three members of the natriuretic peptide receptor family have been identified by molecular cloning. The atrial natriuretic peptide receptor type A (ANPRA) (20), also referred to as GC-A (5), is a membrane form of guanylyl cyclase that directly synthesizes the intracellular second messenger cyclic GMP (cGMP) in response to extracellular hormone binding. This receptor responds to stimulation by ANP and BNP (3,5,20,32) but is not a hormonal target for CNP stimulation (1Sa). A second receptor/guanylyl cyclase homologous to ANPRA, referred to as ANPRB (3) for cGMP stimulation (15a). The third receptor in this family, termed ANPRC (10,19), is homolog...

Neutral Endopeptidase Inhibition Potentiates the Effects of Natriuretic Peptides in Renin Transgenic Rats.

“…In contrast, in the presence of NEP inhibition, CNP has a natriuretic action in dogs, which is due to inhibition of distal sodium reabsorption without increasing urinary cGMP excretion (50). The reason for our failure to observe an increase in the renal excretion of sodium after infusions of CNP into anesthetized normotensive or hypertensive rats in the present study may be the absence of ANP-B receptors in rat kidneys (39,40), as already mentioned.…”

“…It has also been found that CNP has a much stronger effect than ANP in lowering blood pressure in anesthetized dogs, whereas ANP is more potent in increasing plasma cGMP and the urinary excretion of sodium and cGMP (46). The reason why CNP did not decrease the blood pressure in hypertensive or normotensive anesthetized rats in this study is so far unclear, but a possible explanation could be the absence of ANP-B receptors in rat kidney (39,40) as mentioned above.…”

“…The distribution of ANP-B receptors varies among tissues and among species. Interestingly enough, in hamster and rat glomeruli no cGMP response was seen with CNP (37,38), and no ANP-B receptors have been found in the kidneys of monkeys or rats (39,40). Furuya et al (38) have reported that CNP potently stimulates cGMP production in cultured rat vascular smooth muscle cells.…”

Identification of the atrial natriuretic factor‐RIC receptor subtype (B‐clone) in cultured rat aortic smooth muscle cells

“…The ANF-R~A subtype is mostly specific for both ANF and brain natriuretic peptide (BNP) [3,4] and is found at high concentration in many target organs of these natriuretic peptides [5]. The ANF-R~c subtype is mainly specific for C-type natriuretic peptide (CNP) [2] and its distribution is limited to tissues of neuronal origin [5]. The ANF-Rm subtype, which has not yet been cloned, displays higher affinity for ANF than for BNP [1] and does not recognize CNP.…”

“…The ANF-Rm subtype, which has not yet been cloned, displays higher affinity for ANF than for BNP [1] and does not recognize CNP. The ANF-Rz receptor class, which has been cloned, does not discriminate between these peptides [6], is widely distributed [5] and recognizes biologically inactive ANF derivatives e.g. [CysZt~]rANF-(102-116)x-NH2 (C-ANF).…”