Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. I. Renal alpha 1-, alpha 2-, and beta-adrenergic receptors and their signaling.

Michel, Martin C.; Siepmann, F; Philipp, Thomas; Brodde, Otto‐Erich

doi:10.1161/01.hyp.22.2.169

Cited by 33 publications

(24 citation statements)

References 44 publications

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“…Almost the opposite phenomenon has been observed in age-matched spontaneously hypersensitive rats; G s -S did not change, whereas G s -L significantly decreased in membranes derived from 28-week-old rats (Michel et al 1994). The reduced G s -L content may well be the molecular basis for the previously observed unchanged isoprenaline-stimulated cAMP formation despite the increased -adrenergic receptor number (Michel et al 1993).…”

Section: Kidneymentioning

confidence: 78%

The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory guanine nucleotide-binding protein. Do they behave in an identical way?

Novotný

Svoboda²

1998

Journal of Molecular Endocrinology

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The relative proportions and tissue distribution of the long (G s -L ) and short (G s -S ) variants of the subunit of the stimulatory G-protein (G s ) change under a wide range of metabolic conditions, such as cellular differentiation, ontogenetic development, ageing and various adaptive processes. Although the two variants of G s are generally regarded to be functionally identical, this review summarizes recent experimental support for the non-identical behaviour of these proteins. Similarly, there is no consistent evidence for the functional meaning of these changes as far as regulation of adenylate cyclase activity is concerned. Since it is hard to believe that the complicated scheme of alternative splicing and the energy-consuming synthesis of proteins would be performed for no reason, it is suggested that G s variants might be involved in controlling other effector molecules and processes besides adenylate cyclase and cAMP metabolism. Such an idea is indirectly supported by specific alterations in the G s -L /G s -S ratio under various physiological and pathophysiological conditions.

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Section: Kidneymentioning

confidence: 78%

The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory guanine nucleotide-binding protein. Do they behave in an identical way?

Novotný

Svoboda²

1998

Journal of Molecular Endocrinology

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“…This mechanism is similar to but distinct from homologous desensitization (18,19) because the uncoupling in hypertension is independent of renal dopamine levels (3,16,20). Similarly, the uncoupling is not due to heterologous desensitization because the responsiveness of other G protein-coupled receptors (e.g., parathyroid hormone, ␤-adrenergic, and cholecystokinin receptors) remains intact in the prehypertensive spontaneously hypertensive rat (3,8,(21)(22)(23).…”

mentioning

confidence: 88%

G protein-coupled receptor kinase 4 gene variants in human essential hypertension

Felder

Sanada

et al. 2002

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

249

419

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Essential hypertension has a heritability as high as 30 -50%, but its genetic cause(s) has not been determined despite intensive investigation. The renal dopaminergic system exerts a pivotal role in maintaining fluid and electrolyte balance and participates in the pathogenesis of genetic hypertension. In genetic hypertension, the ability of dopamine and D1-like agonists to increase urinary sodium excretion is impaired. A defective coupling between the D1 dopamine receptor and the G protein͞effector enzyme complex in the proximal tubule of the kidney is the cause of the impaired renal dopaminergic action in genetic rodent and human essential hypertension. We now report that, in human essential hypertension, single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK4␥, increase G protein-coupled receptor kinase (GRK) activity and cause the serine phosphorylation and uncoupling of the D1 receptor from its G protein͞effector enzyme complex in the renal proximal tubule and in transfected Chinese hamster ovary cells. Moreover, expressing GRK4␥A142V but not the wild-type gene in transgenic mice produces hypertension and impairs the diuretic and natriuretic but not the hypotensive effects of D1-like agonist stimulation. These findings provide a mechanism for the D1 receptor coupling defect in the kidney and may explain the inability of the kidney to properly excrete sodium in genetic hypertension.L ong-term regulation of blood pressure is vested in the organ responsible for the control of body fluid volume, the kidney (1, 2). Dopamine facilitates the antihypertensive function of the kidney because it is both vasodilatory and natriuretic (3). Dopamine (produced by renal proximal tubules) via D 1 -like receptors is responsible for over 50% of incremental sodium excretion when sodium intake is increased (3-6). The paracrine͞ autocrine dopaminergic regulation of sodium excretion is mediated by tubular but not by hemodynamic mechanisms (6). The ability of dopamine and D 1 -like agonists to decrease renal proximal tubular sodium reabsorption is impaired in genetic rodent hypertension and human essential hypertension (3,5,(7)(8)(9)(10)(11)(12)(13)(14)(15). Indeed, the aberrant D 1 -like receptor function in the kidney precedes and cosegregates with high blood pressure in spontaneously hypertensive rats. In addition, disruption of the D 1 receptor in mice produces hypertension (12, 13). The pivotal role of dopamine in the excretion of sodium after increased sodium intake has led to the hypothesis that an aberrant renal dopaminergic system is important in the pathogenesis of some forms of genetic hypertension (3,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Several mechanisms potentially responsible for the failure of endogenous renal dopamine to engender a natriuretic effect in genetic hypertension have been investigated and ruled out, including decreased renal dopamine production and receptor expression, aberrant nephron segment distribution of dopamine receptors, defective effector enzymes (adenylyl cyclase or...

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“…Body weight, kidney weight, kidney-to-body weight ratio, and systolic blood pressure of all male rats have been described. 7 In female SHR, body weight (WKY: 258± 1 g, n=29; SHR: 223±2 g, n=39; P<.0001) and kidney weight (WKY: 779±59 mg; SHR: 705±43 mg; /><.0001) were lower than in female WKY; in contrast, kidney-to-body weight ratio …”

mentioning

confidence: 88%

“…4 - 6 We have recently reported that in parallel with blood pressure elevations numbers of a t -, a 2 -, and /3-adrenergic receptors increase in kidneys of spontaneously hypertensive rats (SHR) relative to those of age-matched normotensive Wistar-Kyoto (WKY) rats. 7 Despite increased a r and /3-adrenergic receptor numbers, norepinephrine-stimulated inositol phosphate formation and isoprenaline-stimulated cyclic AMP (cAMP) formation remained unchanged. 7 These data suggest the occurrence of a relative desensitization of renal a r and £-adrenergic receptors during the development of hypertension in SHR.…”

mentioning

confidence: 99%

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Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. II. Renal G proteins in male and female rats.

et al. 1994

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Previously we have reported an increased renal a,-and /3-adrenergic receptor expression in male spontaneously hypertensive rats that occurred ontogeneticalry in parallel with blood pressure elevation. However, increased receptor numbers were not accompanied by enhanced stimulation of inositol phosphate and cyclic AMP formation, respectively, indicating relative desensitization. We have now quantified a-subunits of the G proteins G, (G, ,,"," and G, t^), G,, and G q by immunoblotting and pertussis toxin-catalyzed ADP-ribosylation in renal membranes from 3-, 6-, 8-, and 28-week-old normotensive and spontaneously hypertensive male WistarKyoto rats; additionally, 28-week-old female normotensive and spontaneously hypertensive rats were studied. During ontogenesis of male normotensive rats, G, &" increased, G, r emained unchanged, and G^ and G,,, decreased. In adult normotensive rats no sex differences were detected for G, ^^, G, k.,, and G^. When male rats from the normotensive and T he kidney is the tissue with the greatest long-term impact on blood pressure control because of its infinite gain mechanism. 1 On the other hand, chronically elevated arterial blood pressure affects renal function.2 -3 Renal function is tightly controlled by neurotransmitters and hormones such as catecholamines, angiotensin II, endothelin, vasopressin, and neuropeptide Y, many of which act via G proteins. -6 We have recently reported that in parallel with blood pressure elevations numbers of a t -, a 2 -, and /3-adrenergic receptors increase in kidneys of spontaneously hypertensive rats (SHR) relative to those of age-matched normotensive Wistar-Kyoto (WKY) rats.7 Despite increased a r and /3-adrenergic receptor numbers, norepinephrine-stimulated inositol phosphate formation and isoprenaline-stimulated cyclic AMP (cAMP) formation remained unchanged.7 These data suggest the occurrence of a relative desensitization of renal a r and £-adrenergic receptors during the development of hypertension in SHR./3-Adrenergic receptor coupling to cAMP formation by adenylate cyclase occurs via the stimulatory G protein G, and can be attenuated via the inhibitory G protein G ; .8 aj-Adrenergic receptor coupling to inositol phosphate formation appears to occur via G q and/or G n 9 ; additionally, one or more subtypes of a^-adrenergic receptors may couple to inositol phosphate formaReceived October 21, 1993; accepted in revised form January 24, 1994.From the Department of Medicine, University of Essen, Germany.Correspondence to Dr Martin C. Michel, Nephrol. Lab. IG 1, Klinikum, Hufelandstr 55, D-45122 Essen, Germany. spontaneously hypertensive strains were compared, all G protein a-subunits were similar in the prehypertensive phase (3 weeks). In established hypertension (28 weeks), G, ,"", and G,,, were reduced, whereas G, &,« and G^ remained unchanged. G, fco, was also reduced during the development of hypertension (6 and 8 weeks), whereas G, ^ and G^, were not consistently altered in this phase. The reduction in G, ^^ seen in male adult hypertens...

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Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. I. Renal alpha 1-, alpha 2-, and beta-adrenergic receptors and their signaling.

Cited by 33 publications

References 44 publications

The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory guanine nucleotide-binding protein. Do they behave in an identical way?

The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory guanine nucleotide-binding protein. Do they behave in an identical way?

G protein-coupled receptor kinase 4 gene variants in human essential hypertension

Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. II. Renal G proteins in male and female rats.

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