Effects of an Aldosterone Antagonist, Spironolactone, on Pinealectomized Rats

Karppanen, Heikki; Vapaatalo, Heikki

doi:10.1159/000136251

Cited by 12 publications

(6 citation statements)

References 9 publications

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“…The evidence that implicates the pineal gland and zinc involvement in pressor response [Cunnane et al, 1980al and the reports that suggest an involvement of the pineal gland in hypertension [Zanoboni et al, 1978;Karppanen et al, 19701 may indicate that melatonin, via modulation of zinc levels, is involved to some extent in control of blood pressure. That aldosterone has been suggested to be involved in the pineal gland effects on blood pressure [Karppanen and Vapaatalo, 1971;Gromova et al, 19671 would imply that effects on zinc are not solely responsible for pressor effects but may serve as part of a modulating system. With scant evidence at hand it would be premature to propose any positive interaction between the pineal gland and zinc, but further investigation is certainly warranted.…”

Section: Discussionmentioning

confidence: 99%

Effect of Methoxyindole Administration on Plasma Cation Levels in the Rat

Morton

1989

Journal of Pineal Research

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Administration of methoxyindoles to rats in both the morning and the afternoon caused significant changes in circulating plasma cation levels. All the methoxyindoles except melatonin were without effect at doses below 100 micrograms/kg; the observed changes caused by doses of 100 micrograms/kg can, therefore, probably be best described as pharmacological rather than having physiological significance. Melatonin at all doses tested (25, 50, and 100 micrograms/kg) led to a decrease in plasma magnesium levels 3 h after administration in the morning, and this finding is discussed in the light of a possible feedback mechanism between melatonin and circulating magnesium. Melatonin administration in the afternoon was without effect on magnesium levels. Zinc levels were also decreased significantly 3 h after a morning dose of melatonin (50 and 100 micrograms/kg), and the possible functional significance of this observation is discussed. Most of the observed effects can be considered nonspecific and pharmacological, and further work is needed to fully elucidate the involvement, if any, of the pineal gland in regulation of cations.

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Section: Discussionmentioning

confidence: 99%

Effect of Methoxyindole Administration on Plasma Cation Levels in the Rat

Morton

1989

Journal of Pineal Research

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“…In an earlier report, Karppanen and Vapaatalo [3] found that pinealectomy increased daily urine output in rats. However, in a recent study, an increase in water consump tion and urine production was recorded after melatonin administration in Syrian hamsters [66].…”

Section: Diurnal Studies O F[25i]iodomelatonin Binding Sites In Kidnmentioning

confidence: 91%

“…Melatonin has been found to regulate a vari ety o f functions of the central nervous system and peripheral organs, including the cardio vascular and/or renal systems [ 1], Pinealecto-my resulted in hypertension in anesthetized [2] and unanesthetized rats [3], Such altera tions in vascular parameters have been attrib uted to the lack of circulating melatonin in duced by pinealectomy [4] as melatonin ad ministration reverses the effect of pinealectomy-induced hypertension in rats [5]. In hu mans, there is also evidence that melatonin may have a hypotensive effect in essential hypertensive patients [6], Pinealectomy increased blood pressure and daily urine production.…”

Section: Introductionmentioning

confidence: 99%

[<sup>125</sup>l]lodomelatonin Binding Sites in Mammalian and Avian Kidneys

1993

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[^I25I]Iodomelatonin binding sites have been identified and characterized in kidneys of birds and mammals. These binding sites in the kidneys of guinea pig, duck and chicken were found to be stable, reversible, saturable, specific and of high affinity. The binding densities (B_max) of [¹²⁵I]iodomelatonin binding sites in the kidneys of guinea pig, duck and chicken ranged from 1.07 to 6.43 fmol/mg protein and the equilibrium dissociation constants (K_d) from 19.2 to 44.6 pmol/l at the middle of the light period (mid-light). It appears that [¹²⁵I]iodomelatonin binding in the kidneys of mammalian species may have lower densities compared with birds. In the mammals studied, the guinea pig kidney showed the highest [¹²⁵I]iodomelatonin binding. Pharmacological data indicated that the [¹²⁵I]iodomelatonin binding to kidneys of guinea pig, duck and chicken was highly specific to melatonin, 2-iodomelponin and 6-chloromelatonin. Diurnal variations in the B_max of [¹²⁵I]iodomelatonin binding sites were detected in the kidneys of duck and chicken with no difference in affinity. However, there was no diurnal variation in the K_d or B_max in the guinea pig kidneys. The density of [¹²⁵I]iodomelatonin binding sites in the cortex of guinea pig kidney was more than 8-fold higher than the binding in the medulla. Guanosine 5''-O-(3-thiotriphosphate) (GTPγS; 10 µmol/1) reduced the B_max and increased the K_d of [¹²⁵I]iodomelatonin binding sites in the chicken kidney. However, in the membrane preparations of the guinea pig kidney, co-incubation with GTPγS (15 µmol/l) increased the K_d with no effect on the B_max of the [¹²⁵I]iodomelatonin binding. The effects of GTPγS on the kidney [¹²⁵I]iodomelatonin binding suggest that these binding sites may couple to a G protein. The identification of [¹²⁵I]iodomelatonin binding sites in the kidneys of mammals and birds supports the possibility of melatonin acting directly on the renal system.

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“…In several experiments designed to de crease circulating melatonin levels, a pinealectomy-induced elevation in blood pressure has been reported both in anesthetized [14] and nonanesthetized rats [15,30], Daily urine production was also reportedly increased, with a concomitant decrease in the excretion of sodium and potassium in pinealectomized rats [17]. Changes in plasma sodium concen trations have been reported in association with an increase in circulating levels of cal cium, magnesium and zinc in rats with low circulating melatonin levels following con stant light treatment [31].…”

Section: Comparative Studiesmentioning

confidence: 99%

“…Pineal involvement in the renin-angioten sin-aldosterone system was suggested by the finding of hypertension [14][15][16] and the in crease in daily urine production [17] in pinealectomized rats. The above changes may be mediated by melatonin through a direct or indirect pineal-renal connection.…”

mentioning

confidence: 99%

[<sup>125</sup>I]lodomelatonin-Binding Sites in the Chicken Kidney: Characterization and Comparison to Other Avian Species

Song

Pang

1992

Neurosignals

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The existence of [¹²⁵I]iodomelatonin-binding sites in the kidney of the chicken and other avian species has been demonstrated in the present study. [¹²⁵I]Iodomelatonin-binding sites in membrane preparations of the chicken kidney were reversible, saturable, specific and of high affinity. Scatchard analysis of the specific binding revealed an equilibrium binding constant (K_d) of 30.3 ± 5.1 pmol/l (n = 5) and a total number of binding sites (B_max) of 2.89 ± 0.24 fmol/mg protein (n = 5) at the middle of the light period (mid-light). The Hill coefficient approached 1.0, suggesting a single class of [^I25I]iodomelatonin-binding sites in the chicken kidney. The diurnal variation study showed that the B_max was 52% higher at mid-light than that in the middle of dark period(1.90 ± 0.33 fmol/mg protein, n = 4; p < 0.05), with no significant variation in K_d. The K_d value determined from kinetic analysis was 10.8 pmol/l in the mid-light birds, which was comparable to values determined from equilibrium studies. The competition inhibitor experiments demonstrated that [¹²⁵I]iodomelatonin-binding sites were highly specific for melatonin with the following order of potency: 2-iodomelatonin > melatonin, 6-chloromelatonin > 6-hydroxy-melatonin > N-acetylserotonin ≫ 5-methoxytryptamine, 5-methoxytryptophol, 5-hydroxyindole-3-acetic acid, 5-hydroxytiyptamine, 1-acetylindole-3-carboxaldehyde, 3-acetylindole, tryptamine, 5-methoxyindole-3-acetic acid, L-tryptophan, harmaline, acetylcholine, epinephrine and norepinephrine. Studies on the relative binding density of [¹²⁵I]iodomelatonin to the kidney in different species of birds showed the following descending order: duck > chicken > pigeon > quail. It has been reported that [^I25I]iodomelatonin-binding sites exist in the duck kidney and the possible direct action of melatonin on renal function suggested. The identification of [^l25I]iodomelatonin-binding sites in the chicken and other avian kidneys supports this hypothesis and suggests that [¹²⁵I]iodomelatonin-binding sites are universal in the kidneys of birds.

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Effects of an Aldosterone Antagonist, Spironolactone, on Pinealectomized Rats

Cited by 12 publications

References 9 publications

Effect of Methoxyindole Administration on Plasma Cation Levels in the Rat

Effect of Methoxyindole Administration on Plasma Cation Levels in the Rat

[<sup>125</sup>l]lodomelatonin Binding Sites in Mammalian and Avian Kidneys

[<sup>125</sup>I]lodomelatonin-Binding Sites in the Chicken Kidney: Characterization and Comparison to Other Avian Species

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