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D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 181 records · Page 10Linked to original sources
PubMed1983

The role of prostaglandins in neuroendocrine junctions: studies in the pineal gland and the hypothalamus.

This article discusses current experimental evidence indicating a role for prostaglandins (PGs) in pineal and median eminence neuroendocrine junctions. Both tissues release PGs, particularly of the E series, upon exposure to norepinephrine (NE) and through alpha-adrenoceptors. Exposure of pineal and median eminence explants to nanomolar concentrations of PGE2 augments melatonin and GnRH release, respectively. In the pineal gland, this effect appears to be linked to the stimulation of adenylate cyclase. Both in vivo and in vitro PG synthesis inhibitors impair the hormone release elicited by NE. In the pineal gland, PGE2 also constitutes a trans-synaptic negative signal for NE release. PGs receptors are present in pineal and hypothalamic membranes.

Animals↗
PubMed1983

Characterization of flunitrazepam and beta-carboline high affinity binding in bovine pineal gland.

High affinity binding of 3H-flunitrazepam (FNZP) to crude membrane preparations of bovine pineal membranes was examined by a rapid filtration procedure through Whatman GFB paper. At 0 degrees C binding reached equilibrium in about 20 min. Scatchard analysis of data at equilibrium revealed a single population of binding sites with dissociation constant (Kd) = 3.14 +/- 0.45 nM and binding site concentration (Bmax) = 55.6 +/- 5.6 fmol/mg protein. Kinetic analysis of the association and dissociation curves indicated a kinetic Kd = 1.13 nM, in reasonable agreement to that obtained at equilibrium. When various benzodiazepine (BZP) analogues were tested for their ability to inhibit 3H-FNZP binding, the following Ki (nM) were obtained: clonazepam (0.22), Ro 15-1788 (0.48), FNZP (0.95), Ro 5-4864 (greater than 10,000). When the beta-carboline derivative 3H-ethyl-beta-carboline-3-carboxylate ester (E beta CEE) was used as a radioligand, Kd at equilibrium (0.98 nM), kinetic Kd (1.69 nM) and affinity order for analogues were in close agreement to those found for FNZP binding; however, Bmax was about 60% that observed for 3H-FNZP binding. Addition of GABA or pentobarbital (100 microM) to pineal membranes increased 3H-FNZP binding by 55 and 72%. These results suggest the existence of a mixed population of type 1 and type 2 central BZP receptor subclass in bovine pineal gland.

Animals↗
PubMed1983

The sympathetic superior cervical ganglia as "little neuroendocrine brains".

The superior cervical ganglia (SCG) provide sympathetic innervation to the pineal gland, cephalic blood vessels, the choroid plexus, the eye, carotid body and the salivary and thyroid glands. Removal of the ganglia brings about several neuroendocrine changes in mammals, including the disruption of water balance in pituitary stalk-sectioned rats and the alteration of normal photoperiodic control of reproduction and thyroid function in hamsters, ferrets, voles, rams and goats. These effects are commonly attributed to pineal denervation. However, pinealectomy does not always mimic ganglionectomy in its neuroendocrine sequelae. This paper discusses several examples illustrating the differences in ganglia and pineal removal, including the acute and chronic effects of ganglionectomy on the control of thyroid response to TSH in rats. A functionally relevant link between SCG and the hypothalamus occurs in rats, inasmuch as ganglionectomy depresses norepinephrine uptake and increases the number and responses of alpha-adrenoceptors in medial basal hypothalamus. Lastly the SCG are active points of concurrency for hormone signals, as revealed by the metabolic changes induced by steroid and anterior pituitary hormones in these structures, even in the absence of intact preganglionic connections, as well as by the existence of putative receptors for some of the hormones, namely estradiol, testosterone and corticosteroids. The SCG appear to constitute a peripheral neuroendocrine center.

Adrenal Cortex Hormones↗
PubMed1983

Ipsilateral thyroid growth and depressed thyroid hormone synthesis and content after unilateral superior cervical ganglionectomy in rats.

The role of the sympathetic nervous system in the control of the goitrogenic response was examined in adult male rats subjected to unilateral superior cervical ganglionectomy 12-30 days earlier. A spontaneous goiter as well as an increased thyroid growth after the administration of the goitrogenic agents methylmercaptoimidazole and thyrotropic stimulating hormone (TSH) were found in the ipsilateral lobe. Norepinephrine and epinephrine content decreased significantly by 80 and 31%, and thyroxine (T4) and triiodothyronine (T3) content by 24 and 15%, in the ipsilateral lobe. After the injection of a tracer dose of 125I, percent radioactivity incorporation to diiodotyrosine (DIT) was higher, and that to monoiodotyrosine (MIT) lower, in the ipsilateral lobe; additionally a lower ratio "labeled T3 + T4/labeled DIT" was found in the denervated thyroid lobe. These results suggest that the sympathetic nerve terminals in the thyroid gland modulate the organ's response to circulating TSH.

Animals↗
PubMed1982

Benzodiazepine receptor sites in bovine pineal.

[3H]Flunitrazepam (FNZP) binds to a single class of high affinity binding sites in bovine pineal membranes (KD 2.8 nM). FNZP binding increased by 25% after exposure to gamma-aminobutyric acid and exhibits a high degree of specificity for drugs acting on the central type of benzodiazepine receptor. High affinity binding of [3H]ethyl-3-carboline ester to pineal membranes has a KD 0.8 nM and about 60% of the maximal number of FNZP binding sites.

Animals↗
PubMed1982

Involvement of alpha-adrenoceptors in norepinephrine-induced prostaglandin E2 release by rat pineal gland in vitro.

Rat pineal glands incubated in vitro with 10 or 100 microM norepinephrine (NE) released 51% and 415% more prostaglandin E2 (PGE2) to the medium than in the absence of NE. Phentolamine (10 microM) prevented fully the effect of NE at both concentrations, whereas propranolol failed to affect it significantly. After superior cervical ganglionectomy (SCGx), NE-induced PGE2 release was significantly higher than in sham-operated controls--an effect also blocked by phentolamine but not by propranolol. These results suggest that NE releases PGE2 in rat pineals via alpha-adrenoceptors, acting at a post-synaptic site, and that SCGx induces alpha-adrenergic supersensitivity in the pinealocytes.

Adrenergic Fibers↗
PubMed1982

Pinealectomy advances the time of development of steroid feedback on luteinizing hormone release in immature female rats.

The effect of pinealectomy (Px) on the development of steroid positive feedback on luteinizing hormone (LH) release was examined in female rats subjected to surgery at 10 days of age. Estradiol-progesterone injection decreased serum LH in sham Px or intact controls younger than 20 days, while a significant LH release was found at day 22; Px rats showed a steroid-induced LH depression only at day 16, a positive feedback being detectable at day 20, 2 days earlier than in sham Px or intact rats. Daily injections of 10-50 micrograms melatonin to intact rats disrupted the LH negative feedback response at day 20, and diminished steroid-induced LH release at day 24.

Animals↗
PubMed1982

Circadian rhythm and neural regulation of rat pineal angiotensin converting enzyme.

Angiotensin converting enzyme was detectable in rat pineal gland and exhibited a circadian rhythm in activity with maximum at the end of the light phase of daily photoperiod. Superior cervical ganglionectomy (SCGx) or exposure to light for 6 days increased enzyme activity and obliterated morning-evening differences, whereas injection of the beta-agonist isoproterenol depressed the high values observed in SCGx animals. These results indicate that angiotensin converting enzyme in the pineal gland is under negative control by the norepinephrine released from pineal sympathetic nerves.

Animals↗
PubMed1982

Effects of estradiol on norepinephrine and prostaglandin efflux in medial basal hypothalamus of ovariectomized rats.

The spontaneous and K+-stimulated efflux of norepinephrine (NE) and the release of PGE2 and PGF2 alpha were examined in medial basal hypothalamus (MBH) of ovariectomized rats killed before and during the LH release that follows estradiol treatment. As compared to vehicle-treated, ovariectomized rats, estradiol-primed rats exhibited a 60% more increase in K+-stimulated 3H-overflow of MBH slices preloaded with 3H-NE at morning hours (1000 hours). Estradiol treatment did not result in further increase of K+-induced 3H release from MBH slices at the time of LH release (1700 hours), nor affected labeled NE release in occipital cortex slices. A significant difference between K+-stimulated NE release of vehicle-treated spayed rats killed at 1000 and 1700 hours was observed, the latter showing 54% more release upon stimulus. PGE2 efflux was time-dependent being highest at the evening in both vehicle- and estradiol-treated animals. The MBH of estrogenized rats released significantly more PGE2 at the evening as compared to the controls. The release of PGF2 alpha remained essentially unchanged regardless of estradiol treatment or time of day. The present results offer additional support to the involvement of MBH catecholamines and prostaglandins in the mechanism of LH secretion in the rat.

Animals↗
PubMed1982

Testosterone decreases beta-adrenoceptor sites in rat pineal gland and brain.

Testosterone administration to orchidectomized rats brought about a significant, 55% decrease of beta-adrenoceptor sites in the pineal gland, assessed from the specific binding of radioactive dihydroalprenolol (DHA). The changes in density of binding sites were not accompanied by significant modifications of the Kd. FSH or LH treatment of acutely castrated animals did not affect pineal beta-adrenoceptor binding. The depressive effects of testosterone in beta-adrenergic receptors were also observed in crude membrane fractions of medial basal hypothalamus and cerebral cortex. Sympathetic denervation of the pineal gland by superior cervical ganglionectomy did not abolish the changes in pineal beta-adrenoceptor density caused by testosterone. Hormone effects did not depend on a direct effect of the hormone on beta-adrenoceptor sites because testosterone did not compete with [3H]-DHA for the binding sites, in vitro. These results suggest that testosterone depresses pineal beta-adrenergic sites by acting mainly on postsynaptic sites.

Animals↗
PubMed1982

Effect of pentoxifylline on alpha- and beta-adrenoceptor sites in cerebral cortex medial basal hypothalamus and pineal gland of the rat.

The intraperitoneal injection of the methylxanthine derivative pentoxifylline (3,7-dimethyl-1-(5-oxo-hexyl)-xanthine] brought about, 3 hr later, a significant depression of alpha- and beta-adrenoceptor sites in the cerebral cortex, and of beta-adrenoceptor sites in medial basal hypothalamus and pineal gland, (assessed from the specific binding of radioactive dihydroergocryptine and dihydroalprenolol respectively). The changes in the density of binding sites were not accompanied by significant modifications of the Kd's. Sympathetic denervation of the pineal gland by superior cervical ganglionectomy (SCGx) abolished the changes of beta-adrenoceptor number in the pineal caused by pentoxifylline. The increase of alpha-adrenoceptor sites in the hypothalamus brought about by ganglionectomy was not affected by injection of pentoxifylline. Pentoxifylline did not compete in vitro for radioligand binding to brain membranes. These results suggest that methylxanthines depress brain adrenoceptor sites acutely, probably by down-regulation of receptors following the increase in catecholamine release caused by injection of the drug.

Animals↗
PubMed1982

Norepinephrine stimulates testosterone aromatization and inhibits 5 alpha reduction via beta-adrenoceptors in rat pineal gland.

The possible modulatory role of the sympathetic nervous system on testosterone aromatization and 5 alpha reduction by rat pineal gland was examined in vitro. NE (10 microM) added to pineal organ cultures increased by 72% the conversion of [14C]testosterone into estradiol and depressed by 39 and 53% that into the 5 alpha-reduced metabolites 5 alpha-dihydrotestosterone (5-DHT) and 5 alpha-androstanediol (5 alpha-diol). Both effects of NE were negated by the addition of the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Dibutyryl cAMP (0.1 mM) mimicked the effect of NE on pineal [14C]testosterone metabolism; it also mimicked the NE-induced inhibition of [14C]progesterone reduction to 5 alpha-pregnanedione and 3 alpha-hydroxy-5 alpha-pregnan-20-one by rat pineal gland explants. At the end of the dark phase of the daily photoperiod, pineal aromatization of testosterone was significantly higher, and 5 alpha reduction lower, than in rats killed at noon. Pineal glands obtained from rats subjected to superior cervical ganglionectomy 12 h earlier exhibited increased conversion of [14C]testosterone into estradiol, and depressed synthesis of 5 alpha-reduced metabolites, as compared with their respective sham-operated controls. 3 days after ganglionectomy a diminished testosterone aromatization was found. These results suggest that the increased release of NE from pineal sympathetic nerve endings stimulates testosterone aromatization and inhibits 5 alpha reduction via a beta-adrenoceptor.

5-alpha Reductase Inhibitors↗
PubMed1982

Role of prostaglandins in rat pineal neuroeffector junction. Changes in melatonin and norepinephrine release in vitro.

The effects of prostaglandins (PGs) on melatonin secretion and norepinephrine (NE) and release in rat pineal gland were examined in vitro. To study melatonin secretion, pineal explants were incubated for 6 h in tissue culture 199 medium with 1-1000 nM PGE1, PGE2, or PGF2 alpha. melatonin concentration in pineal glands and media was determined by RIA, PGE2 increased pineal and medium melatonin at all concentrations tested, with a maximum of 1 nM; PGE1 was effective only at concentrations 100-1000 times greater, whereas 100 nM PGF2 alpha gland. Exposure of pineal explants to 10 microM NE brought about a 20-fold increase in melatonin release to the medium. This effect was impaired significantly, but not blocked, by prior exposure to indomethacin, acetylsalicylic acid, or mefenamic acid at supramaximal concentrations to inhibit PG synthesis (100 microM). To examine the effects of PGs on NE release, endogenous NE stores in pineal nerve endings were labeled in vitro by incubating rat pineals with [3H]NE for 30 min. Fifty minutes later, at the time when spontaneous radioactivity efflux had leveled off, transmitter release was elicited by a 1-min exposure to 80 mM K+ (S1), and the stimulus was repeated 35 min later (S2). PGs (10-100 nM) were added to the medium 20 min before S2. Ratios between fractional release of the two consecutive stimulations (S2/S1) varied between 0.84 and 1.16 in control pineals. Only 100 nM PGE2 impaired significantly transmitter release by 40%. These results suggest that PGE2 can play a role in NE-stimulated melatonin synthesis. At greater concentrations PGE2 inhibits NE release from pineal nerve endings.

Alprostadil↗