Failing human ventricular cardiomyocytes contain functional beta 2-adrenergic receptors. Canine myocytes also contain functional beta 2-adrenergic receptors. The canine ventricular response to beta 2-agonists is increased in tachypacing failure. Positive inotropic responses to beta 2-stimulation are not mediated by increases in cAMP or cAMP-dependent phosphorylation of phospholamban.
Exchangeable intracellular Ca2+ as measured by 45Ca2+ uptake more than doubled when isolated adult rat ventricular cardiomyocytes were incubated 30 min with 8 microM cyclosporin; nevertheless the cells retained a normal rod-shaped morphology. High concentrations of ouabain caused a similar increase in 45Ca2+ uptake, but in this case the Ca2+ overload caused nearly all cells to hypercontract into a round disorganized form. The response to cyclosporin was concentration dependent with an apparent half-maximal effective concentration of 0.5 microM for enhancement of net 45Ca2+ accumulation. Verapamil (1 microM) could not inhibit this cyclosporin effect, but it was abolished by a 5-min preincubation with 12 microM crude ruthenium red. Cyclosporin also decreased the rate of 45Ca2+ efflux from prelabeled myocytes into Ca(2+)-containing and Ca(2+)-free media. These data are consistent with inhibition of mitochondrial 45Ca2+ efflux through the cyclosporin-sensitive mitochondrial inner membrane pore. It would appear that periodic transient increases in mitochondrial inner membrane permeability provide a pathway for mitochondrial Ca2+ extrusion under relatively normal conditions in isolated adult rat heart cells.
ABSIRACT Kidney homogenates from adult male Japanese quail or chickens demonstrate hydroxylase activity predominantly for the 24 rather than the 1 position of 25-hydroxyvitamin D3 (25-hydroxycholecalciferol There is abundant clinical evidence that sex hormones play an important role in calcium metabolism (1, 2). The widespread problem of postmenopausal osteoporosis must be related in part to an estrogen-androgen deficiency. The many attempts to define the role of estrogen in bone have indicated that it is involved in bone remodeling, but have not defined its mechanism of action (1, 2). Birds present a special case of calcium metabolism because of the necessity of shell production during the egg-laying phase of their lives. Riddle et al. (3) observed that serum calcium rises and calcium retention increases in female pigeons prior to the initiation of ovulation; such changes are not observed in the male. The retained calcium is deposited in medullary bone, from which it can be mobilized during egg shell formation (4). Castrated male birds given estrogen alone become hypercalcemic, but they do not retain calcium (4); whereas, when they receive both estrogen and androgen, they become hypercalcemic and retain calcium in medullary bone (4). Thus, it is clear that both estrogen and androgen are involved in calcium utilization in birds and its retention in medullary bone.The utilization and retention of calcium and phosphorus in birds is under direct control of vitamin D (5), and vitamin D is the precursor of the hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; vitamin D3 = cholecalciferol], which apparently directs the utilization of calcium and phosphorus (6, 7). This hormone is synthesized in the kidney from 25-hydroxyvitamin D3 (25-OH-D3), the major circulating metabolite of vitamin D, which is synthesized in the liver from vitamin D3 itself. The production of 1,25-(OH)2D3 by the kidney is tightly regulated; the 25-OH-D3-1-hydroxylase [= 25-hydroxycholecalciferol 1-monooxygenase; 25-hydroxycholecalciferol, Abbreviations: 1,25-(OH)2D3, 1,25-dihydroxyvitamin D3; 25-OH-D3, 25-hydroxyvitamin D3; 24R,25-(OH)2D3, 24R,25-dihydroxyvitamin D3.
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