Kiyoshi Kurokawa

Actions of 1,25-Dihydroxycholecalciferol in Patients with Hypophosphatemic, Vitamin-D-Resistant Rickets

Abstract 1,25-dihydroxycholecalciferol, the active form of vitamin D, was administered orally in doses of 1.3 to 2.7 μg per day to four patients with hypophosphatemic, vitamin-D-resistant rickets t...

Distribution of prostaglandin E2-sensitive adenylate cyclase along the rat nephron

To define sites of prostaglandin action of renal tubules, the distribution of adenylate cyclase sensitive to prostaglandin E2 (PGE2) was examined in single nephron segments dissected from rat kidney. Further, the interaction between PGE2 and vasopressin on adenylate cyclase activity in nephron sensitive to vasopressin was evaluated. Procedures involved in isolating nephron segments were without effects on adenylate cyclase stimulation by PGE2. PGE2 stimulated adenylate cyclase activity of the thin descending limb of Henle (tDL), cortical collecting tubules (CCT), and medullary collecting tubules (MCT) at concentrations of 1.4 x 10(-5) to 2.8 x 10(-5) M. PGE2 was without effects in other nephron segments tested including proximal convoluted tubules, proximal pars recta, the thin and thick ascending limb of Henles loop, and distal and connecting tubules. PGE2, at both high (2.8 x 10(-5) M) and low (2.8 x 10(-8) M) concentrations, did not inhibit adenylate cyclase activity stimulated by submaximal doses of vasopressin in medullary thick ascending limb of Henle (MTAL), CCT, and MCT. These data define the distribution of PGE-sensitive adenylate cyclase in the rat nephron, i.e., tDL, CCT, and MCT, and show the lack of direct inhibitory actions of PGE2 on vasopressin sensitive adenylate cyclase in MTAL, CCT, and MCT.

Evidence for two separate adenyl cyclase systems responding independently to parathyroid hormone and -adrenergic agents in the renal cortex of the rat.

Summary Parathyroid hormone (PTH), isoproterenol and norepinephrine stimulated adenyl cyclase activity of rat renal cortex. The effects of the latter two were abolished by propranolol but not by phentolamine. The effects of PTH were not influenced by these adrenergic blocking agents. Stimulation of the enzyme activity by a maximal dose of PTH was 3–4 times greater than that by a maximal dose of isoproterenol and the effects of both agonists were additive. These results indicate that in rat renal cortex there are two discrete adenyl cyclase systems responding independently to PTH and catecholamines, and the receptor for the latter agents being a beta adrenergic receptor.

Effect of parathyroid hormone and calcium ions on substrate oxidation by isolated glomeruli of the rat.

Effect of Ca2+ and parathyroid hormone (PTH) on 14 CO2 production from certain metabolic substrates by isolated glomeruli of rat kidney were examined. Increasing calcium concentration in the incubation medium inhibited 14CO2 production from 14C-labeled alpha-ketoglutarate and succinate, stimulated 14CO2 production from [1-14C]glucose and [1-14C]glutamate, but was without effect on that from [6-14C]glucose. PTH in the presence but not in the absence of Ca2+ inhibited 14CO2 production from labeled alpha-ketoglutarate and glutamate but not from labeled glucose. Additions of cyclic AMP as well as hormonal agents known to act directly on the glomureli, such as histamine, epinephrine, prostaglandin E2, vasopressin, angiotensin II and insulin, did not alter 14 CO2 production from labeled alpha-ketoglutarate. These data show the presence of calcium-dependent inhibitory actions on PTH on oxidation of alpha-ketoglutarate and glutamate which may be independent of cyclic AMP. These metabolic effects of PTH may underlie the alteration in the glomerular ultrafiltration coefficient and glomerular filtration induced by the hormone.

Early Renal Adaptation to Dietary Phosphorus Restriction

An important consequence of dietary phosphorus (P) restriction is the ability of the kidney to virtually clear the urine of phosphate (Pi) (1). This adaptation can occur in the normal, thyroparathyroidectomized (1), and vitamin D-deficient state (2). The adaptation has been demonstrated in isolated perfused proximal tubules (3) as well as in vesicles formed by tubule brush border membranes (BBM) of proximal tubules (4, 5), and has been demonstrated as early as two days in renal BBM of the pig (6). The underlying mechanism for this renal adaptation is unknown. Several reports have suggested that an increased alkaline phosphatase (A1Pase) in the BBM is responsible for increased Pi reabsorption during P-depletion (4, 5). Other studies suggest that the adaptation may occur without concomitant changes in AlPase and there is no causal relationship between the two phenomena (7, 8, 9). The present study was designed to assess how rapid renal adaptation by BBM vesicles (BBMV) to dietary P-restriction develops and whether significant changes in BBM AlPase activity occur prior to changes in BBMV Pi transport. The results demonstrate that Pi uptake by the BBMV increases within 4 hours after dietary P restriction preceding any detectable increase in the AlPase.

Effect of Parathyroid Hormone on the Isolated Papillary Muscle of the Rat Heart

It has been well accepted that the bone and the kidney are the principal organs of parathyroid hormone (PTH) action. Several lines of evidence obtained during the last decade suggest that PTH directly acts on organs other than the bone and kidney; these include the brain, liver and blood cells (1–5).

Metabolic and endocrine alterations in end-stage renal failure

Many alterations in metabolic and endocrine function occur in end-stage renal disease. Glucose intolerance is almost always present with uremia; it improves shortly after institution of regular hemodialysis. Hyperlipidemia (type IV) is prevalent, and atherosclerotic cardiovascular disease causes death in about 50% of patients receiving long-term hemodialysis. Although plasma levels of growth hormone usually are elevated, children with chronic renal failure show growth retardation. The occurrence of thyroid disorders is difficult to determine, since many clinical features of uremia are similar to those of hyperthyroidism and hypothyroidism. The incidence of duodenal ulcer is high, possibly due to high gastrin levels. Sex hormone disturbances are common. Anemia is a constant feature of chronic renal failure; patients usually tolerate it well.