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D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 145 records · Page 8Linked to original sources
PubMed1987

Melatonin, 5-methoxytryptamine and some of their analogs as cyclo-oxygenase inhibitors in rat medial basal hypothalamus.

Melatonin, and its analogs 6-chloro- and 6-fluoromelatonin inhibited in a dose-dependent way (10(-8)-10(-5) M) labeled prostaglandin (PG) E2, PGF2 alpha, thromboxane (Tx) B2 and 6-keto-PGF1 alpha production from [14C]arachidonate by rat medial basal hypothalamus (MBH). 5-Methoxytryptamine also depressed arachidonate metabolism; at 10(-8) M concentrations the effect of 5-methoxytryptamine on PGE2, PGF2 alpha and TxB2 synthesis (93-96% inhibition), and 6-keto-PGF1 alpha (75% inhibition) was greater than that observed for melatonin (51-56% and 44% inhibition, respectively). Neither 6-hydroxymelatonin nor serotonin affected MBH cyclo-oxygenase pathway in vitro.

5-Methoxytryptamine↗
PubMed1987

In vitro effect of neuropeptide Y on melatonin and norepinephrine release in rat pineal gland.

1. To study neuropeptide Y (NPY) effect on melatonin production, rat pineal explants were incubated for 6 hr with 10-1,000 nM NPY in the presence or absence of 10 microM norepinephrine (NE). Melatonin content in the pineal gland and media was measured by radioimmunoassay (RIA). 2. NPY (10-1,000 nM) increased melatonin production and, at 10 or 100 nM concentrations (but not 1,000 nM), enhanced NE stimulation of melatonin production. 3. NPY (1,000 nM) impaired 3H-labeled transmitter release induced by a K+ depolarizing stimulus in rat pineals incubated with 3H-NE. 4. These results suggest that NPY affects both pre- and postsynaptic pineal mechanisms.

Animals↗
PubMed1987

Cellular and molecular mechanisms controlling melatonin release by mammalian pineal glands.

1. The pineal gland is regulated primarily by photoperiodic information attaining the organ through a multisynaptic pathway initiated in the retina and the retinohypothalamic tract. 2. Norepinephrine (NE) released from superior cervical ganglion (SCG) neurons that provide sympathetic innervation to the pineal acts through alpha1- and beta 1- adrenoceptors to stimulate melatonin synthesis and release. 3. The increase in cyclic AMP mediated by beta 1-adrenergic activation is potentiated by the increase in Ca2+ flux, inositol phospholipid turnover, and prostaglandin and leukotriene synthesis produced by alpha 1-adrenergic activation. 4. Central pinealopetal connections may also participate in pineal control mechanisms; transmitters and modulators in these pathways include several neuropeptides, amino acids such as gamma-aminobutyric acid (GABA) and glutamate, and biogenic amines such as serotonin, acetylcholine, and dopamine. 5. Secondary regulatory signals for pineal secretory activity are several hormones that act on receptors sites on pineal cells or at any stage of the neuronal pinealopetal pathway.

Adrenergic Fibers↗
PubMed1987

Neuroendocrine integrative mechanisms in mammalian pineal gland: effects of steroid and adenohypophysial hormones on melatonin synthesis in vitro.

The time course for the decrease in norepinephrine concentration of rat pineal explants in culture indicated a significant fall starting at the 4th hour and completed after 16-24 h of incubation. Significant decreases of serotonin and 5-hydroxyindoleacetic acid (HIAA) levels in tissue, an increase of HIAA/serotonin ratio, and an increase of melatonin production rate in vitro were also observed as a function of the incubation time. Estradiol (10(-7)-10(-5) M) increased rat pineal melatonin content, testosterone (10(-5) M) decreased it and progesterone was devoid of activity when incubated with explants for up to 6 h. The in vitro stimulatory effect of estradiol on rat pineal methoxyindole synthesis was blocked by propranolol but not by phentolamine; propranolol also blocked the increase of nuclear estradiol-receptor complex produced by estrogen exposure of pineal explants. TSH (1-100 ng/ml), growth hormone (10-100 ng/ml) and LH (10 ng/ml) augmented rat pineal melatonin content while 100 ng/ml of FSH decreased it significantly. Prolactin exerted a biphasic effect on rat pineal explants, the lowest concentration augmenting melatonin content while the high concentration depressed it. Deep, intermediate and superficial segments of guinea-pig pineal glands showed an increase in melatonin concentration after a 6-h incubation in the presence of 10(-7)-10(-5) M estradiol.

Animals↗
PubMed1987

In vitro effects of adenohypophysial hormones on rat pineal melatonin content and release.

The effect of adenohypophysial hormones on rat pineal melatonin content and release was examined in vitro. Medium concentration of radioimmunoassayable melatonin decreased after a 6 h exposure to 1-100 ng/ml FSH; pineal levels of melatonin were only decreased by 100 ng/ml FSH. LH (1-100 ng/ml) augmented significantly medium melatonin concentration, tissue levels being increased at 10 ng/ml LH. Parallel increases of explant and medium melatonin content were found after exposure to 1-100 ng/ml TSH. At the smallest concentration employed (1 ng/ml) prolactin increased melatonin content and release while at 100 ng/ml a significant depression of both parameters was found. Growth hormone (1-10 ng/ml) augmented melatonin levels in medium but failed to modify them at 100 ng/ml, although at this concentration tissue melatonin levels increased. ACTH did not modify pineal melatonin synthesis in vitro.

Adrenocorticotropic Hormone↗
PubMed1987

Involvement of 5-lipoxygenase pathway in norepinephrine stimulation of rat pineal melatonin synthesis.

The effect of lipoxygenase inhibition, leukotriene agonists and antagonists, and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) was examined in the rat pineal gland in organ culture. To study melatonin secretion pineal explants were incubated for 6 h in tissue culture medium 199 with the different drugs. Melatonin concentration in the pineal gland and the medium was measured by RIA. Exposure of explants to norepinephrine (NE) brought about a 2- to 5-fold increase in both parameters, an effect that was reduced but not abolished, by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 10(-5) M). Lilly 171883 (10(-5) M) or FPL 55712 (10(-5) M; both antagonists of leukotrienes) reduced NE-induced melatonin production. Neither NDGA nor Lilly 171883 affected melatonin production in the absence of NE. Leukotrienes C4 and D4 increased melatonin release to the media at all concentrations tested (1-1,000 nM) with a maximum effect at 1 nM (leukotriene C4) and 10 nM (leukotriene D4). Significantly higher tissue melatonin concentrations as compared to controls were observed after exposure of pineal explants to 1 and 100 nM of leukotriene C4, or 100 nM of leukotriene D4. Another 5-lipoxygenase metabolite, 5-HETE, increased pineal melatonin content at concentrations of 1, 10 and 100 nM whereas only 1,000 nM stimulated melatonin release. These results suggest that the 5-lipoxygenase pathway plays a significant role in NE-stimulated melatonin production by the rat pineal gland.

Acetophenones↗
PubMed1987

Autonomic nervous system regulation of murine immune responses as assessed by local surgical sympathetic and parasympathetic denervation.

The effect of local sympathetic denervation on immune responses of submaxillary lymph nodes (SmLN) of mice was examined in animals subjected to unilateral superior cervical ganglionectomy (SCGx). Norepinephrine (NE) content in ipsilateral SmLN decreased by 90% 7-20 days after SCGx, while bilateral SCGx resulted in a 91% decrease of SmLN NE content. SmLN of mice subjected to unilateral SCGx exhibited greater plaque-forming cell (PFC) response than the innervated contralateral SmLN, when challenged i.d. or i.p. with sheep red blood cells (SRBC) 10-20 days after surgery. In mice challenged with SRBC at an early phase of sympathetic nerve paralysis (i.e., 2 h after SCGx), PFC response was already increased in the ipsilateral SmLN whereas during the anterograde degeneration of nerve endings (6-24 h after SCGx) an impending depression of PFC number was observed. Contact hypersensitivity and allogeneic delayed-type reactions were also enhanced in the ear ipsilateral to SCGx. Primed SmLN cells of nodes located ipsilaterally to SCGx, when injected to (BALB/c x C57BL/6) F1, resulted in significantly higher spleen index than similarly treated, contralateral SmLN. In contrast, mitogenic stimulation under various experimental protocols failed to reveal significant differences between proliferation of cell populations obtained from ipsilateral and contralateral SmLN of unilaterally SCGx mice. SmLN of mice parasympathetically decentralized by unilateral sections of the chorda tympani-lingual nerve trunk showed lower PFC response than the innervated contralateral SmLN, when challenged with SRBC 8-28 days after surgery. These results suggest a regulatory function of the autonomic nervous system in immune reaction.

Animals↗
PubMed1986

Melatonin increases in vivo GABA accumulation in rat hypothalamus, cerebellum, cerebral cortex and pineal gland.

The effect of melatonin on in vivo gamma-aminobutyric acid (GABA) accumulation in several brain regions was determined by measuring the increase of GABA levels following inhibition of GABA transaminase. A single melatonin injection (25-300 micrograms/kg) augmented significantly, by 17-20%, GABA accumulation in the hypothalamus and caused a dose-dependent increase of this parameter in the pineal gland. Significant rises of GABA accumulation were found in the cerebellum and cerebral cortex after administering 100-300 and 300 micrograms/kg of melatonin, respectively.

4-Aminobutyrate Transaminase↗
PubMed1986

Binding and effects of catecholestrogens on adenylate cyclase activity, and adrenoceptors, benzodiazepine and GABA receptors in guinea-pig hypothalamic membranes.

Catecholestrogen (CE) binding to guinea-pig hypothalamic membranes was assessed by using [3H]2-hydroxyestrone (2-OHE1) as a ligand. Binding was maximal at pH 7.4 and 37 degrees C, and after 10 min incubations. A high affinity binding site with dissociation constant (KD) = 0.20 +/- 0.02 nM and site concentration (Bmax) = 38 +/- 2 fmol/mg protein, and a low affinity binding site with KD = 235 +/- 10 nM and Bmax = 4.2 +/- 1.0 pmol/mg protein (n = 7) were detected. The order of affinity (Ki, microM) for displacement of 10 nM [3H]2-OHE1 from hypothalamic binding sites was 2-OHE1 (0.8), 2-hydroxyestradiol (2-OHE2) (1.0), epinephrine (5.9), norepinephrine (NE) (7.7), dopamine (270), estradiol, estrone, propranolol, phentolamine, domperidone (greater than 10 000). NE inhibition of 2-OHE1 binding was non-competitive, Only 0.5 mM 2-OHE2 depressed in a non-competitive way the hypothalamic beta-adrenoceptor binding (measured by using [3H]dihydroalprenolol) without affecting alpha-adrenoceptor binding (measured by using [3H]dihydroergocryptine). Both 2-OHE2 and 2-OHE1 impaired NE-stimulated adenylate cyclase activity in hypothalamic membranes with EC50 of about 5 and 10 microM, respectively. CE decreased [3H]gamma-aminobutyric acid binding by hypothalamic membranes with Ki = 8 microM (2-OHE2) and 50 microM (2-OHE1). The binding of [3H]flunitrazepam to the same membrane preparation was not affected by CE. These results support the existence of significant CE binding and effects in guinea-pig hypothalamic membranes.

Adenylyl Cyclase Inhibitors↗
PubMed1986

Changes in growth hormone and prolactin release after superior cervical ganglionectomy of rats.

Superior cervical ganglionectomy (SCG X) decreased significantly serum growth hormone (GH) levels in rats 14-96 h after surgery, during and immediately after anterograde degeneration of regional sympathetic terminals. At later times (up to 28 days after SCG X) an increase in serum GH was observed. SCG X augments prolactin (PRL) release, but only at the earliest time examined (14 h after surgery). Injection of the alpha-adrenoceptor blocker, phenoxybenzamine, but not of the beta-blocker, propranolol, negated the depression in serum GH found in SCG X rats 14 h after surgery, without affecting PRL release.

Animals↗
PubMed1986

Origins of the sympathetic projections to rat thyroid and parathyroid glands.

The present study aimed to characterize the localization and pathways of sympathetic neurons innervating the thyroid and parathyroid glands. In rats subjected to unilateral superior cervical ganglionectomy or unilateral decentralization of the superior cervical ganglion 7 days earlier, ipsilateral depression of thyroid norepinephrine (NE) and epinephrine content to 6-16% of the contralateral intact lobe was observed. In both groups of animals neuronal [3H]NE uptake by the ipsilateral thyroid lobe was suppressed. In unilaterally decentralized rats pineal catecholamine levels remained within normal values whereas in unilaterally ganglionectomized rats a 74% decrease of pineal NE and E content was found. Unilateral section of the external carotid nerve abolished, as did unilateral superior cervical ganglionectomy, neuronal [3H]NE uptake in the ipsilateral thyroid lobe. In contrast external carotid nerve section did not modify the neuronal uptake of [3H]NE in the pineal gland. Either unilateral superior cervical ganglionectomy or external carotid nerve section resulted in similar involution of ipsilateral thyroid lobes of hypophysectomized rats. These results indicate that postganglionic sympathetic perikarya innervating the thyroid-parathyroid territory are located in the middle and/or inferior cervical ganglia and send their axons through the SCG and the external carotid nerve to these glands.

Animals↗
PubMed1986

Early inhibition and changes in diurnal rhythmicity of the pituitary-thyroid axis after superior cervical ganglionectomy of rats.

The effect of superior cervical ganglionectomy (SCGx) on the pituitary-thyroid axis was examined in rats. SCGx decreased serum thyrotropin (TSH) and thyroxine (T4) levels for up to 4 days after surgery, during and immediately after completion of anterograde degeneration of regional sympathetic terminals. At later times TSH levels in control and SCGx rats did not differ, but a significant increase of serum T4 was found two weeks after SCGx. A diurnal rhythm in serum TSH and T4 levels with maxima at 11.00 h (TSH) and at 14.00 and 22.00 h (T4) was found in sham-operated rats 3 days after surgery. At this time SCGx evoked a general depression of TSH levels as well as a shift of 3 h in their maximum. A similar shift of the afternoon peak and abolition of the nocturnal peak in serum T4 were detectable in SCGx rats. In SCGx animals examined during anterograde nerve degeneration, i.e. 14 h after surgery, injection of the alpha 1-adrenoceptor blocker phenoxybenzamine negated denervation-induced changes of TSH and counteracted partially T4 effects. The beta-adrenergic blocker propranolol did not modify serum TSH levels in SCGx rats but further decreased serum T4 concentration. Treatment with both drugs simultaneously did no affect TSH release compared to SCGx, phenoxybenzamine-treated rats but effectively decreased serum T4. These results further support the involvement of superior cervical ganglion neurons in the control of thyroid function.

Animals↗
PubMed1986

Diurnal variations of benzodiazepine binding in rat cerebral cortex: disruption by pinealectomy.

In a previous work, pinealectomy was found to depress benzodiazepine (BZP) receptor binding in cerebral cortex membranes of rats killed at noon. In order to assess the effect of pineal removal on diurnal variations of BZP binding site concentration and affinity, groups of intact, pinealectomized, or sham-pinealectomized rats (subjected to surgery 2 wk earlier) were killed at six different time intervals during the 24-h cycle. BZP binding was assessed by Scatchard analysis of 3H-flunitrazepam high-affinity binding to cerebral cortex membranes. In intact and sham-pinealectomized rats, a maximum in BZP receptor concentration was found at midnight. Pinealectomy blunted the nocturnal peak of receptor concentration and caused a significant depression of binding site number at noon. No changes in the affinity of the binding sites for the radioligand were detected as a function of time of day or following surgery. In a dose-response experiment for melatonin ability to restore the depressed BZP receptor concentration of cerebral cortex membranes of pinealectomized rats killed at noon, a minimal effective dose of 25 micrograms/kg body weight was obtained. These results further support a link between pineal activity and brain BZP receptors in rats.

Animals↗
PubMed1986

In vitro effects of estradiol, testosterone, and progesterone on 5-methoxyindole content, cyclic adenosine 3',5'-monophosphate synthesis, and norepinephrine release in different parts of the female guinea pig pineal complex.

To examine the effects of estradiol, testosterone, or progesterone on cyclic adenosine 3',5'-monophosphate (AMP) accumulation, 5-methoxyindole levels, and norepinephrine (NE) release by the female guinea pig pineal complex, samples of the deep, intermediate, or superficial portions of the complex were incubated in vitro with varied concentrations of either hormone. Exposure for 10 minutes to physiological amounts of estradiol (10 nM) or to 100 microM NE increased significantly cyclic AMP levels to the same extent in the three pineal regions. A maximal effect on cyclic AMP accumulation was observed at 100-nM concentrations of estradiol, with a tendency to return to basal levels at 1-10 microM of estradiol. Only high concentrations of testosterone or progesterone (i.e., 1-10 microM) increased cyclic AMP accumulation in incubated guinea pig pineal fragments. At a 100-nM concentration estradiol did not affect NE-stimulated cyclic AMP accumulation in guinea pig pineal fragments. In samples of either pineal region incubated for 6 hours in TC 199 medium with 10(-7) M or greater concentrations of estradiol and analyzed for melatonin, 5-methoxyindoleacetic acid, and 5-methoxytryptophol by high-pressure liquid chromatography with electrochemical detection, a significant increase of melatonin levels was found. Neither testosterone nor progesterone modified 5-methoxyindole levels of incubated explants. K+-stimulated transmitter release from guinea pig pineal fragments previously incubated with 3H-NE was not affected by hormone exposure. These results suggest that physiological concentrations of estradiol may exert a postsynaptic stimulation of cyclic AMP and melatonin synthesis to the same extent in all three regions of the female guinea pig pineal complex.

Animals↗
PubMed1986

Changes in gamma-aminobutyric acid high affinity binding to cerebral cortex membranes after pinealectomy or melatonin administration to rats.

In order to assess the effect of pinealectomy (Px) on the diurnal rhythmicity of gamma-aminobutyric acid (GABA) high affinity binding to cerebral cortex membranes, groups of intact, Px or sham Px rats (subjected to surgery 15 days earlier) were killed at six different time intervals during the 24-hour cycle. GABA binding was estimated by Scatchard analysis of 3H-GABA binding to cerebral cortex membranes prepared from individual brains; only one type of binding site with dissociation constant (KD) about 20-50 nM and site number (Bmax) about 200-500 fmol/mg protein was apparent in the assay conditions employed. In intact and sham Px rats Bmax attained minimal values at night and increased during daylight. Px increased generally Bmax and disrupted its normal diurnal rhythmicity, a peak in Bmax being observed at midnight. A significant decrease of GABA high affinity binding affinity was detected at morning hours in intact rats and at late scotophase and morning hours in Px and sham Px rats. Bmax of GABA high affinity binding in Px rats attained maximal values by 5-10 days after surgery and decreased somewhat 5 days later. Sham Px rats exhibited a transient increase in Bmax up to 10 days after surgery, returning to normal values by the 15th day. Superior cervical ganglionectomy increased binding affinity up to 15 days after surgery without affecting Bmax. The minimal melatonin effective dose to counteract Px-induced increase of GABA high affinity binding was 25 micrograms/kg body weight when given 3 h before sacrifice. Melatonin activity on GABA binding did not depend upon a direct effect on the binding sites, as shown in vitro. These results suggest a link between pineal function, melatonin secretion and GABA receptor activity in rats.

Animals↗
PubMed1986

Changes in calcitonin release during sympathetic nerve degeneration after superior cervical ganglionectomy of rats.

To assess the role of peripheral sympathetic nerves in the regulation of calcitonin release, rats subjected to superior cervical ganglionectomy (SCGx) 16-28 h earlier were used. The time periods selected allowed us to examine C cell response during the supraliminal release of sympathetic transmitter that accompanies anterograde degeneration of nerve varicosities as well as during the neural paralysis that ensues thereafter. At the time intervals examined, SCGx did not result in significant changes of basal serum calcitonin or Ca levels. The intraperitoneal administration of CaCl2 brought about an impending increase of serum Ca to the same extent in SCGx and sham-operated rats. A significant depression of calcitonin release was observed in rats killed around the time of nerve terminal degeneration (16-21 h post SCGx) but not about 10 h later. Additionally a delay to achieve a maximal calcitonin response was apparent during nerve degeneration. Injection of the alpha-adrenoceptor blocker phenoxybenzamine significantly increased basal calcitonin levels and restored the depressed calcitonin response to hypercalcemia seen in SCGx rats. Treatment with the beta-adrenoceptor-blocker propranolol counteracted phenoxybenzamine activity but was unable to modify per se calcitonin release in SCGx or sham-operated rats. Basal Ca levels and their increase after intraperitoneal CaCl2 were similar in all examined groups regardless of the drug injected. In an additional experiment phenoxybenzamine injected into SCGx rats in doses one-fifth those employed earlier still reversed both the depression in maximal calcitonin response as well as the delay to attain maximal release after CaCl2, but was unable to affect basal calcitonin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Interaction between alpha- and beta-adrenoceptors in rat pineal adenosine cyclic 3',5'-monophosphate phosphodiesterase activation.

The adrenergic regulation of the low-Km pineal cAMP phosphodiesterase (PDE) activity was studied in adult female rats. PDE activity showed a transient enhancement (up to 42%) during the process of degeneration of pineal sympathetic nerve terminals that followed superior cervical ganglionectomy (SCGx), thus confirming the neural modulation of the enzyme. Treatment with isoproterenol (0.3-5.0 mg/Kg) increased significantly PDE activity within 2 hours. Phenylephrine induced a significant increase of pineal PDE only at a 10 mg/Kg dose, while at a lower dose (1 mg/Kg) it potentiated the stimulatory effect of isoproterenol. Treatment of pineal organ cultures with 100 microM propranolol inhibited norepinephrine (NE)-induced PDE activity while 100 microM phentolamine had no significant effect. Propranolol at doses unable to alter the in vitro NE-induced stimulation of pineal PDE activity (1 microM), antagonized such NE effect when used in combination with 1 microM phentolamine. At equimolecular concentrations (1 microM) the mixed alpha-beta-adrenergic agonist NE was more effective than the beta-adrenergic agonist isoproterenol to increase pineal PDE in vitro. These results suggest an alpha-beta-adrenergic interaction in the sympathetic modulation of low-Km PDE activity of rat pineal gland.

3',5'-Cyclic-AMP Phosphodiesterases↗