Calcium transport, direct effect

Alternative explanations have been considered to determine whether lead can induce hypertension in the absence of chronic renal disease [47, 51]. One postulated mechanism involves an alteration in intracellular calcium concentration by lead so as to cause an increased tonic contraction of arterioles leading to hypertension. Others have suggested a direct effect of lead on juxtaglomerular cells leading to an increase in renin secretion. Others have suggested alterations in renal ion transport, particularly relating to an effect of lead on sodium potassium ATPase. 

Conrad and Hepler [61] found that a subclass of voltage-gated calcium channels, L-type channels sensitive to dihydropyridines (DHP), were involved. DHP agonists induced bud initials in the absence of cytokinin while the DHP antagonist blocked bud formation even in the presence of cytokinin. Agonists did not promote complete bud development suggesting that cytokinins have other effects as well. Direct measurements of uptake in moss protoplasts demonstrated the existence of DHP-sensitive calcium transport... 

Olson, E.B., DeLuca, H.F. 25-Hydroxycholecalciferol direct effect on calcium transport. Science 165, 405-407 (1969)... 

Considerable progress was made in elucidating the biotransformations of cholecalciferol (Vitamin D3) to biologically active forms. The first of these has been identified as 25-hydroxy cholecalciferol, which in turn is further metabolized to the 1,25 and perhaps also to the 21,25-dihy-droxy derivatives. Control over calcium transport is assured, since the initial hydroxylation Is obligatory in conferring biological activity and the biosynthesis of the active metabolites Is controlled by feedback regulation. Whiie these hydroxyiated derivatives, unlike Vitamin D3 itself, are all directly effective at the cellular level, there is some evidence... 

Cardiac glycosides cause a positive inotropic effect which means an increase of the cardiac beat volume by enhanced contraction ability. The reason for this is supposed to be aligned with the direct inhibition of the transport enzyme sodium/ potassium-ATPase. The decrease of sodium ions enhances the calcium ion concentration, which activates the myofibrillic enzyme and inactivates proteins like tropo-myocine and tropomine. Till present, a final proof for this hypothesis is lacking, the toxicity, however, is definitely aligned with these effects [97]. 

Voltage-gated calcium-channel and receptor-gated calcium channel are two channels that have the reverse effects of PMCA. They transport the calcium influx following the calcium gradients regulated directly by the electric potential between the two sides of plasma membrane or receptor binding, respectively. ... 

Cell death induced by AmB in the medullary thick ascending limb is prevented by ouabain [108]. A reasonable explanation for this observation is that ouabain, by inhibiting transport, decreases the oxygen demand of an area of the nephron that already has a hmited oxygen supply. This is consistent with the observation that AmB exhibits preferential damage to the medullary ray, an area that is vulnerable to hypoxic injury [48]. It is also conceivable that AmB-induced renal vasoconstriction and ischemia to this section of the nephron enhances cell death produced by a direct toxic action. Thus, any maneuver that improves renal perfusion, or decreases oxygen demand, would be expected to be protective. This may explain the salutary effect of salt loading, theophylline, calcium channel... 

Thiazides and the related diuretics inhibit the transport of sodium in the early distal tubules, which results in the enhanced elimination of sodium, chloride, and water. Potassium and sodium bicarbonate elimination is also enhanced calcium excretion is decreased, uric acid is retained. Glomerular filtration rate is decreased. The antihypertensive effects may be the result of direct arteriolar dilation but the full mechanism has not been identified. 

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