1.Effect of amiloride with or without hydrochlorothiazide on urinary calcium and saturation of calcium salts.
Leppla D, Browne R, Hill K, Pak CY. J Clin Endocrinol Metab. 1983 Nov;57(5):920-4.
To assess the therapeutic role of amiloride in calcium nephrolithiasis, seven patients with renal stones were evaluated before and after 1 month of treatment each with amiloride (2.5 mg twice daily), hydrochlorothiazide (25 mg, twice daily), and both drugs at the same dosages. Although amiloride alone reduced urinary calcium in only two patients, it caused a slightly more prominent decline in urinary calcium when added to hydrochlorothiazide treatment in five patients. The urinary saturation of stone-forming salts (brushite and calcium oxalate) decreased significantly during treatment with hydrochlorothiazide alone or in combination with amiloride. Although the decrease in brushite saturation was slightly more marked with the combined treatment, the reduction in calcium oxalate saturation was equivalent during the two treatment phases. Although serum potassium was significantly reduced during combined treatment with amiloride and hydrochlorothiazide, this reduction was not as prominent as that occurring during treatment with hydrochlorothiazide alone.
2.Inhibitory effects of amilorides on pinealocyte adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate accumulation: possible involvement of postreceptor mechanisms.
Ho AK1, Lalh SS, Young I, Cragoe EJ Jr, Chik CL. Endocrinology. 1990 Jul;127(1):460-6.
In rat pinealocytes, alpha 1-adrenergic receptor activation increases intracellular pH (pHi) through Ca2+/protein kinase-C-dependent activation of the Na+/H+ antiporter. Using a series of amiloride analogs, norepinephrine stimulation of cGMP accumulation is also found to be pHi dependent. In this study, we examined the postreceptor mechanisms involved in the amiloride effects on cyclic nucleotide accumulation using agents that simulate alpha 1-adrenoceptor activation. Four amiloride analogs, with a 500-fold difference in their inhibitory potency of the Na+/H+ antiporter, were used. 5-(N,N-Hexamethylene)amiloride (HA), the most active inhibitor of the Na+/H+ antiporter, had a stimulatory effect on isoproterenol (ISO)-stimulated cAMP, while its effect on cGMP was inhibitory. The other three amiloride derivatives had no effect on the ISO-stimulated cAMP or cGMP responses. All four amilorides (at 10 microM) had no effect on the phenylephrine potentiation of cAMP responses in beta-adrenergically stimulated cells, while they inhibited the potentiation of cGMP accumulation according to their inhibitory potency on the Na+/H+ antiporter.