Studies with Pinealectomized Rats

Karppanen, Heikki; Vapaatalo, Heikki; Lahovaara, S; Paasonen, M. K.

doi:10.1159/000136065

Cited by 44 publications

(23 citation statements)

References 8 publications

(9 reference statements)

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“…data]. Interest ingly, pinealectomy in the rat resulted in a small, but significant increase in blood pressure [25,26]. This increase could be overcome by MT injections [27].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Melatonin Receptors in the Rat Area postrema: Modulation of Affinity with Cations and Guanine Nucleotides

Laitinen

Flügge

Saavedra³

1990

Neuroendocrinology

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We have localized and characterized the binding of the melatonin agonist, 2-[¹²⁵I]iodomelatonin, in the rat area postrema (AP), by using quantitative autoradiography in vitro. At equilibrium conditions, Scatchard analysis revealed saturable high-affinity binding to a single class of sites (Ka 45.9 ± (SE) 6.0 pM and B_max 30.8 ± 4.6 fmol/mg protein, n = 4 experiments with a total of 18 rats). Melatonin and 6-hydroxymelatonin were potent displacers of 2-[¹²⁵I]iodomelatonin binding in the AP (IC50 20 and 500 pM, respectively) while N-acetylserotonin exhibited only a modest potency (IC50 25 nM). Micromolar concentrations of guanine nucleotides dose-dependently and specifically inhibited agonist binding at 22 ° C. Saturation studies revealed that this was due to a decrease in binding affinity. Divalent cations (4 mM CaCl₂ or 2 mM MgCl₂) had no detectable effect on the affinity of the binding site, whereas physiological concentrations of NaCl significantly decreased the binding affinity. These results demonstrate specific high-affinity binding sites for 2-[¹²⁵I]iodomelatonin in the rat AP and suggest coupling of these putative receptors to guanosine nucleotide binding regulatory protein(s).

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“…data]. Interest ingly, pinealectomy in the rat resulted in a small, but significant increase in blood pressure [25,26]. This increase could be overcome by MT injections [27].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Melatonin Receptors in the Rat Area postrema: Modulation of Affinity with Cations and Guanine Nucleotides

Laitinen

Flügge

Saavedra³

1990

Neuroendocrinology

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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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“…That pineal melato nin synthesis could be altered in SHR was additionally demonstrated by the higher nocturnal surge in circulating melatonin concentrations in young SHR, when hyperten sion is not fully developed [8]. In addition, hypertension produced in rats by pinealectomy can be prevented by melatonin administration [9,10].The study of the melatonin system has been recently expanded with the identification, using the melatonin an alogue 2-[l25I]-iodomelatonin [11] and quantitative auto radiography [12][13][14][15][16], of specific, high-affinity melatonin receptors. In an attempt to further understand the physio logical role of melatonin in an animal model of hyperten-…”

mentioning

confidence: 99%

Differential Expression of Melatonin Receptors in Spontaneously Hypertensive Rats

Viswanathan

Laitinen²,

Saavedra³

1992

Neuroendocrinology

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Quantitative autoradiography was used to compare melatonin receptors in brain areas and arteries of young (4 weeks old) and adult (14 weeks old) spontaneously hypertensive rats (SHR) to those in age-matched normotensive controls, Wistar-Kyoto (WKY) rats. Age and strain influenced the number of melatonin receptors in an anatomically selective manner, and the most striking changes occurred in arterial receptors. Melatonin receptors were not detectable in the anterior cerebral arteries of adult SHR. In the caudal artery, melatonin receptors decreased with age in both strains, but the decrease was more pronounced in SHR. When compared to age-matched WKY rats, the number of caudal artery receptors was higher in young and lower in adult SHR. The number of melatonin receptors was higher in the area postrema of adult SHR when compared to adult WKY rats, but in the suprachiasmatic nucleus, no such differences between the two strains were present. Alterations in receptor density were not accompanied by changes in binding affinity. Our results indicate that in the rat melatonin receptors show different developmental patterns according to location and that the receptors may be expressed differentially in genetic hypertension.

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Studies with Pinealectomized Rats

Cited by 44 publications

References 8 publications

Characterization of Melatonin Receptors in the Rat Area postrema: Modulation of Affinity with Cations and Guanine Nucleotides

Characterization of Melatonin Receptors in the Rat Area postrema: Modulation of Affinity with Cations and Guanine Nucleotides

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

Differential Expression of Melatonin Receptors in Spontaneously Hypertensive Rats

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