Type B Atrial Natriuretic Peptide Receptor in Cardiac Myocyte Caveolae

Doyle, Donald D.; Ambler, S. Kelly; Upshaw-Earley, J.; Bastawrous, Amir L.; Goings, Gwendolyn E.; Page, Ernest W.

doi:10.1161/01.res.81.1.86

Cited by 39 publications

(31 citation statements)

References 14 publications

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“…Blood volume expansion as a result of increased venous return to the heart would stretch the cardiac myocytes activating oxytocin release from them just as can occur for ANP release (25). OT released locally by paracrine or autocrine activation of the OT receptors would release ANP that in turn acts on its receptors to activate guanylyl cyclase and reduce intracellular calcium release (26). The decreased intracellular calcium concentration would produce a negative inotropic and chronotropic response that rapidly would reduce cardiac output and, thereby, affect blood volume.…”

Section: Discussionmentioning

confidence: 99%

Rat heart: A site of oxytocin production and action

Jankowski

Hajjar

Kawas

et al. 1998

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

171

134

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We report here that the rat heart is a site of oxytocin (OT) synthesis and release. Oxytocin was detected in all four chambers of the heart. The highest OT concentration was in the right atrium (2128 ؎ 114 pg͞mg protein), which was 19-fold higher than in rat uterus but 3.3-fold lower than in the hypothalamus. OT concentrations were significantly greater in the right and left atria than in the corresponding ventricles. Furthermore, OT was released into the eff luent of isolated, perfused rat heart (34.5 ؎ 4.7 pg͞min) and into the medium of cultured atrial myocytes. Reverse-phase HPLC purification of the heart extracts and heart perfusates revealed a main peak identical with the retention time of synthetic OT. Southern blots of reverse transcription-PCR products from rat heart revealed gene expression of specific OT mRNA. OT immunostaining likewise was found in atrial myocytes and fibroblasts, and the intensity of positive stains from OT receptors paralleled the atrial natriuretic peptide stores. Our findings suggest that heart OT is structurally identical, and therefore derived from, the same gene as the OT that is primarily found in the hypothalamus. Thus, the heart synthesizes and processes a biologically active form of OT. The presence of OT and OT receptor in all of the heart's chambers suggests an autocrine and͞or paracrine role for the peptide. Our finding of abundant OT receptor in atrial myocytes supports our hypothesis that OT, directly and͞or via atrial natriuretic peptide release, can regulate the force of cardiac contraction.Vasopressin and oxytocin (OT) are synthesized predominantly in the magnocellular neurons of the supraoptic nucleus and paraventricular nucleus as well as in the parvocellular neurons within the paraventricular nucleus as parts of larger precursor molecules (1). The precursors are modified posttranslationally and are transported to the posterior pituitary, where the final bioactive peptide products are stored until they are released into the blood stream. Despite being the first peptide hormone to be characterized and synthesized, the effects of oxytocin long were considered to be restricted to stimulation of uterine contractions during labor and milk ejection during lactation. However, OT is found in equivalent concentrations in the neurohypophysis and plasma of both sexes, which suggests that it also may have other physiological roles (2). Moreover, in the central nervous system, OT-containing axons terminate in several brain stem nuclei known to be involved in cardiovascular control, suggesting a potential role for OT in central cardiovascular regulation (3, 4). Indeed, decreased blood pressure may be observed in response to oxytocin given intracerebroventricularly (5), and the inhibition of brain OT synthesis by an antisense oligonucleotide increased blood pressure in rats (6). In primates or humans, the administration of oxytocin often is associated with a decrease in blood pressure (7,8). Peripherally injected OT decreases mean arterial pressure in rats by unknown mec...

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Section: Discussionmentioning

confidence: 99%

Rat heart: A site of oxytocin production and action

Jankowski

Hajjar

Kawas

et al. 1998

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

171

134

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“…39 Neuregulin receptor erbB4 has been localized to caveolae of neonatal ventricular myocytes. 40 Natriuretic peptide receptor type B 41 and monocarboxylate transporter (MCT1) 42 have been immunohistochemically localized to myocyte caveolae in situ. Most recently, activated adenosine A 1 receptors have been shown to translocate out of adult rat ventricular myocyte caveolae on agonist binding.…”

Section: Discussionmentioning

confidence: 99%

Dystrophin Associates With Caveolae of Rat Cardiac Myocytes

Doyle

Goings

Upshaw-Earley

et al. 2000

Circulation Research

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Abstract-The possibility of an interaction between the cytoskeletal protein dystrophin and cell surface caveolae in the mammalian myocardium was investigated by several techniques. Caveolin (cav)-3-enriched, detergent-insoluble membranes isolated from purified ventricular sarcolemma by density-gradient fractionation were found to contain dystrophin and dystroglycan. Further purification of cav-3-containing membranes by immunoprecipitation using anti-cav-3-coated magnetic beads yielded dystrophin but not always dystroglycan. Electron microscopic analysis of precipitated material revealed caveola-sized vesicular profiles that could be double-labeled with anti-dystrophin and anti-cav-3 antibodies. In contrast, immunoprecipitation of membranes with anti-dystrophin-coated beads yielded both cav-3 and dystroglycan. Electron microscopic analysis of this material showed heterogeneous membrane profiles, some of which could be decorated with anti-cav-3 antibodies. To confirm that dystrophin and cav-3 were closely associated in cardiac myocytes, we verified that dystrophin was also present in immunoprecipitated cav-3-containing membranes from detergent extracts, as well as in sonicated extracts of purified ventricular myocytes. Confocal immunofluorescence microscopy of ventricular and atrial cardiac myocytes showed that the cellular distributions of cav-3 and dystrophin partially overlapped. Immuno-electron micrographs of thin sections of rat atrial myocytes revealed a fraction of dystrophin molecules that are in apparently close apposition to caveolae. These results suggest that a subpopulation of dystrophin molecules interacts with cardiac myocyte caveolae in vivo and that some of the dystrophin is engaged in linking cav-3 with the dystroglycan complex. Key Words: heart Ⅲ myocyte Ⅲ caveolae Ⅲ dystrophin T he flask-shaped plasma membrane-associated vesicles called caveolae are non-clathrin-coated organelles first described by Palade in 1953. 1 Recently, caveolae have been proposed to be multifunctional organelles that, in diverse cell types, participate in one or more of the following: as sites for concentration and subsequent internalization of small molecules and as binding sites for Ca 2ϩ ions, 2 as the loci of multiple signal-transducing molecules, 3 and as sites of cytoskeletal attachment to the plasma membrane. 4 Presumptive caveolar properties or "markers" include the caveolar coat protein caveolin (cav), an 18-to 24-kDa protein (depending on the isoform), 5 and a high concentration of cholesterol and sphingolipids. 6 Four isoforms of caveolin encoded by 3 distinct genes have so far been identified. Cav-1␣, 7 also known as VIP21 or VCAV, 8 is found in a variety of tissues, as is cav-1␤, a truncated version also derived from the same gene. 9 cav-2, the isoform most abundant in fat cells, coexpresses with cav-1 in many nonmuscle tissues, 10 whereas cav-3, 11 or MCAV, 12 is found predominantly if not exclusively in muscle cells. Thus, in the heart, cav-3 is the isoform expressed in cardiac myocytes and vascular smooth...

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“…Caveolin-3 over-expression induces cardiac degeneration, fibrosis and cardiac-function impairment, along with DAPC downregulation [123]. ANP is found in rat-cardiomyocyte caveolae [124]. ANP modulates cardiac hypertrophy and remodeling; ANP deficiency exaggerates hypertrophy and remodeling after pressure overload [125].…”

Section: Pathophysiological Implicationsmentioning

confidence: 99%

Involvement of lipid rafts and caveolae in cardiac ion channel function

Maguy

Hébert

Nattel

2006

Cardiovascular Research

187

146

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A variety of lipid microdomains, including caveolae, have been shown to play an important role in both protein targetting and in controlling protein-protein interactions. There is increasing evidence for significant ion channel localization in lipid rafts. Cardiac channel subunits known to localize in lipid rafts include Kv1.4, Kv1.5, Kv2.1, Kv4, Kir2, Kir3, K(ATP), Nav and Cav subunits. This article reviews what is known about the occurrence and functional significance of cardiac ion channel/lipid raft interactions. Much remains to be learned about this area of potentially enormous importance to cardiac function in health and disease.

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Type B Atrial Natriuretic Peptide Receptor in Cardiac Myocyte Caveolae

Cited by 39 publications

References 14 publications

Rat heart: A site of oxytocin production and action

Rat heart: A site of oxytocin production and action

Dystrophin Associates With Caveolae of Rat Cardiac Myocytes

Involvement of lipid rafts and caveolae in cardiac ion channel function

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