Immunohistochemical localization of 3′:5′-cyclic AMP and 3′:5′-cyclic GMP in rat renal cortex: Effect of parathyroid hormone

Douša, Thomas P.; Barnes, Larry D.; Ong, Shu-Hui; Steiner, Alton L.

doi:10.1073/pnas.74.8.3569

Cited by 47 publications

(23 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The slight increase in cGMP in glomeruli appears to be in basic agreement with our previous findings of increased immunoreactive cGMP primarily in glomeruli in the PTH-perfused kidney (17). It should be stressed, however, that changes in cGMP levels found in present experiments are minor, and the interpretation should be extremely guarded.…”

Section: Discussionsupporting

confidence: 79%

See 1 more Smart Citation

Modulation of Cyclic Nucleotides in Isolated Rat Glomeruli

et al. 1978

Self Cite

View full text Add to dashboard Cite

A B S T R A C T Because glomerular functions are modulated by numerous humoral agents, probably acting through cyclic nucleotides, the effects of some polypeptide hormones and biogenic amines on cyclic AMP (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) were studied in glomeruli isolated from rat renal cortex. Glomeruli and cortical tubules were prepared by a combination of sieving and density-gradient centrifugation. Under basal conditions, the contents of cAMP and cGMP in glomeruli were significantly higher than in tubules and unfractionated renal cortical tissue.Histamine caused a striking increase in cAMP in glomeruli (+A% 675±87) and, to a lesser degree, increased cAMP in tubules (+A% 103+25) or in tissue slices. This stimulation was dose-dependent in the range of 1 ,uM-1 mM histamine. Metiamide (an H2-antagonist), but not pyrilamine (an H,-antagonist) blocked the effect of histamine on cAMP, which indicates that histamine causes its effect via interaction with H2 receptors. Histamine caused less extensive increases in cGMP in both glomeruli and tubules. Carbamylcholine caused a marked increase in cGMP in glomeruli (+A 295±7) and a much lower increase in tubules (+A% 70+20); these effects were blocked by 1334atropine. Parathyroid hormone (1 ug/ml) increased cAMP and, to a much lesser degree, also cGMP in glomeruli. In tubules, parathyroid hormone caused nmuch more extensive increases in cAMP than in glomeruli; no changes, or rather a small decline in cGMP, was observed. Angiotensin-I1 (2 uM) markedly lowered cAMP in glomeruli (-A% -45±8) and in tubules (-A% 33±7) but had no effect on cGMP. Bradykinin (20 ,M) did not consistently influience either cAMP or cGMP in glomeruli or tubules.Present results demonstrate that cAMP and cGMP metabolism in glomeruli are controlled independently by humoral agents known to alter glomerular functions in vivo. Our findings are consistent with the view that histamine and cholinergic agents generated and (or) released locally in glomeruli or in their vicinity may play important roles as mediators of immunopathological injury of glomeruli, and that these effects are mediatecl by cAMP and (or) cGMP through interaction with H2 receptors and muscarinic receptors. Likewise, our results suggest that the effects of angiotensin-II and parathyroid hormone on glomerular dynamics may be mediated by cyclic nucleotides.Thus, we surmise that extrarenal as well as intrarenal humoral agents may play an important role in the pathology and physiology of glomeruli through mediation of either cAMP, cGMP, or both. INTRODUCTIONIt has become increasingly evident in recent years that many extrarenal and intrarenal humoral agents mraymodulate diverse aspects of glomerular function (1). For example, the administration of agents such as para- thyroid hormone (PTH)' (2), angiotensin (3, 4), bradykinin, acetylcholine (5,6), and others (1) causes changes in glomerular microcirculation, hydraulic permeability, or in the ultrafiltration properties of glomerular membrane. Perhaps more importantly,...

show abstract

Section: Discussionsupporting

confidence: 79%

“…Cyclic nucleotide phosphodiesterases in glomeruli preferentially hydrolyze cGMP rather than cAMP (15), and are regulated differently than analogous tubular enzymes (16). Immunohistochemical analysis indicated the presence of cAMP or cGMP in glomeruli and their increase in response to PTH (17).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Cyclic Nucleotides in Isolated Rat Glomeruli

et al. 1978

Self Cite

View full text Add to dashboard Cite

show abstract

“…It agents increase glomerular cyclic AMP levels by stimulating adenylate cyclase activity, and that insulin may modulate cyclic nucleotide levels in various tissues by interacting with other peptide and amine hormones (17)(18)(19)(20)(21)(22). It is possible, therefore, that insulin may affect glomerular cyclic nucleotide levels.…”

Section: Resultsmentioning

confidence: 99%

Binding of 125I-insulin to the isolated glomeruli of rat kidney.

Kurokawa¹,

Silverblatt²,

Klein³

et al. 1979

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T To investigate a possible action of insulin on the glomerulus, the binding 1251-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22°C, '251-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was <25% of total binding. A small fraction of '25I-insulin was degraded during incubation. This binding was specific to insulin in that it was inhibited by unlabeled porcine and beef insulins and to a lesser extent by porcine proinsulin and desalanine-desasparagine insulin, but not by glucagon, parathyroid hormone, vasopressin, calcitonin, and angiotensin II. Increasing concentrations of nonlabeled insulin displaced 1251-insulin binding in a dose-dependent fashion. Scatchard plot of the data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that demonstrate negative cooperativity. The addition of excess nonlabeled insulin to the glomeruli preincubated with 1251-insulin resulted in a rapid dissociation of -70% of bound I251-insulin. Insulin decreased the increments in glomerular cyclic AMP levels by epinephrine and by prostaglandin E2, but not those by histamine. These data showed the presence of specific insulin receptors in the glomeruli, and that insulin action may be, at least in part, through modulation of glomerular cyclic AMP concentrations. Such action of insulin may underlie the alteration in glo-

show abstract

“…Administration of cAMP has been shown to mimic the phosphaturic effect of PTH in vivo (4,30), and in vitro (3,15). An increase in adenylate cyclase activity and accumulation of intracellular cAMP after PTH administration have been demonstrated (16,26). The intracellular accumulation of cAMP and subsequent leakage from the renal tubular cells is considered to be an explanation for the increase in urinary excretion of CAMP, and thus, the latter change has been used as an indicator of the renal responsiveness to PTH (3,8,22,32).…”

Section: Resultsmentioning

confidence: 99%

Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

et al. 1981

View full text Add to dashboard Cite

SummaryThe response to parathyroid hormone (PTH) and calcitonin (CT) was studied in eight children with various bone diseases by determining the serum calcium (Ca) and phosphate (P) concentration, urinary phosphate excretion rate, renal phosphate clearance, the percentage of filtered phosphate reabsorbed by the renal tubule (%TRP), creatinine clearance (Ccr), urinary cyclic adenosine 3',5' monophosphate excretion rate (UcA~pV), and urinary cyclic guanosine 3',5' monophosphate excretion rate (Ucc~pV). Administration of PTH caused no significant change in serum Ca and P values, whereas CT produced a decrease ih Ca (A Ca, -1.4 + 0.1 mg/100 ml) and P (AP; -1.1 + 0.1 mg/100 ml). There was an increase in U c~~p V ( A U r~~p V ; 437 74 nmoles/min/100 ml Ccr) without any significant change in UcCMpV after administration of PTH. Phosphaturia was produced by both PTH (A TRP, -18 k 3%) and CT (ATRP, -13 -t 2%). However, CT did not elicit any increase in either U c~~p V or U c~~p V . SpeculationParathyroid hormone (PTH) and calcitonin (CT) induce phosphaturia of a similar magnitude whereas PTH alone increased the urinary excretion of cyclic adenosine 3',5' monosphosphate (CAMP). The phosphaturia induced by CT may not be mediated by a similar mechanism involving the adenylate cyclase-CAMP system as demonstrated for PTH.Parathyroid hormone (PTH) and calcitonin (CT) have opposing effects on bone resorption; PTH induces hypercalcemia by stimulating bone resorption whereas CT induces hypocalcemia by inhibiting bone resorption. Despite their opposing effects on bone, they both act on the kidney to produce phosphaturia. The actions of PTH and CT on both bone and kidney are presumably mediated through the adenylate cyclase cyclic adenosine 3',5'-monophosphate (CAMP) system. Studies have shown increased renal formation and urinary excretion of cAMP in response to PTH (1 I, 12). This change in the urinary excretion of cAMP is considered a qualitative indicator of the effect of PTH on the kidney (8,22,32). Some studies also have shown an increase in the formation of cAMP in the kidney after CT administration (20,27). However, few studies have investigated urinary excretion of cAMP after CT administration, and those that are available, report conflicting results. No increase in urinary excretion of cAMP was reported after CT administration in parathyroiaectomized rats, dogs (I I), and in one patient with hypoparathyroidism (28), whereas an increase in cAMP was reported in hamsters (23) and parathyroidectomized rats (24). Some studies in man (1, 2, 28) have shown an increase in urinary cAMP in response to salmon or porcine CT, but the magnitude of rise was insignificant when compared to the rise after PTH. Therefore, to assess the relationship of urinary cAMP excretion and the phosphaturic response to CT in man, we have studied the effect of synthetic human CT on patients with various bone diseases, all of whom had normal phosphaturic and cAMPuric responses to PTH. In view of the possible role of cyclic guanosine 3',Sf-monophosphate (c...

show abstract

Immunohistochemical localization of 3′:5′-cyclic AMP and 3′:5′-cyclic GMP in rat renal cortex: Effect of parathyroid hormone

Abstract: Adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP)

Cited by 47 publications

References 25 publications

Modulation of Cyclic Nucleotides in Isolated Rat Glomeruli

Modulation of Cyclic Nucleotides in Isolated Rat Glomeruli

Binding of 125I-insulin to the isolated glomeruli of rat kidney.

Urinary Excretion of Cyclic Nucleotides and Phosphate in Response to Parathyroid Hormone and Calcitonin in Man

Contact Info

Product

Resources

About