To investigate the participation of the pineal gland and its hormone melatonin on Na(+)-K(+)-ATPase (the sodium pump) in rat brain, we used Scatchard plots to analyze the changes in rat cerebral cortex of [3H]ouabain high-affinity binding in groups of intact, pinealectomized (PX), and sham-PX rats. Only one type of binding site, with a dissociation constant of approximately 3 nM and site number (Bmax) of approximately 250 fmol/mg protein, was apparent with our assay conditions. PX or sham-PX rats (subjected to surgery 15 days earlier) were killed at six different time intervals during the 24-h cycle. Intact and sham-PX animals showed a similar biphasic pattern in diurnal rhythm of ouabain binding, with a minimal concentration of binding sites at 1600 h and a maximal concentration at 0400 h. Pinealectomy induced a significant increase in Bmax at all time intervals studied, with the largest rise appearing at night and coinciding with the nocturnal peak, whereas the daytime minimum was blunted. Time-dependent experiments indicated that the Bmax of ouabain high-affinity binding in PX rats attained maximal values at 7 days after surgery and decreased somewhat 7 days later, while sham-PX animals showed only a small transient increase in Bmax up to 7 days after surgery, with values returning to normal by the 15th day. Melatonin administration at a single subcutaneous dose of 25 micrograms/kg body wt given 3 h before death was enough to counteract the PX-induced increase of ouabain high-affinity binding. Melatonin was able to enhance the binding of [3H]ouabain to its receptor site, increasing binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
Possible interactions of ACTH-like peptides with melatonin regulation of central-type benzodiazepine (BNZ) receptors have been studied by means of highaffinity 3H-fiunitrazepam binding to rat cerebral cortex membrane preparations. Intracerebroventricular injections of melatonin produce a dose-dependent increase in Bmax in pinealectomized rats, without changes in KD. Analogous effects were obtained after intracerebroventricular injection of melatonin in adrenalectomized and in adrenalectomized plus pinealectomized rats, which indicated the lack of participation of adrenal steroids in this response. Moreover, intracerebroventricular injection of ACTH1–10 induced a similar dose-dependent increased Bmax in sham-operated animals, whereas pinealectomy, but not adrenalectomy, partially counteracted this effect of ACTH1–10 administration. Besides, simultaneous injection of ACTH1–10 plus melatonin reverses the effects of pinealectomy, resulting in an additive effect of both compounds on Bmax. The response obtained when using ACTH4–10 was somewhat different, because no dose response was obtained in any experiment. Although lack of endogenous melatonin partially reduced the increasing effect of ACTH4–10 on Bmax, there were no additive effects at the different doses used. The results strongly suggest that ACTH-like peptides, in addition to melatonin, play a role in regulating central-type rat BNZ receptors.
The role of the pituitary-adrenal axis on receptor binding and diurnal rhythmicity of benzodiazepines (BNZ) was assessed in the rat cerebral cortex. Groups of intact, adrenalectomized (ADx) and/or hypophysectomized (HPx) rats were killed at six different time intervals during the 24-hour cycle. BNZ binding was estimated by Scatchard analysis of 3H-flunitrazepam high-affinity binding to rat cerebral cortex. Intact and sham ADx animals show a similar pattern in diurnal thythm of BNZ binding, with a maximal concentration at midnight. Bilateral ADx induced a significant increase in Bmax at all time intervals studied, the largest rise appearing at midnight. HPx alone led to a slightly smaller rise in Bmax than in ADx rats, while HPx performed in ADx rats did not modify the response to ADx alone. Bmaχ of BNZ binding in ADx rats reached maximal values at 3–7 days after surgery, and decreased somewhat at 15 days post-ADx. Corticosterone administration at a single dose of 5 mg i.p. 24 h before sacrifice returned Bmax to normal values in ADx as well as in ADx plus HPx rats. The corticosterone effect is not exerted on the BNZ binding sites themselves, as revealed by the lack of effect of this glucocorticoid in vitro. These findings indicate that BNZ receptors in rat cerebral cortex can be modified by the adrenal gland, with corticosterone as a primary effector.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.