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Biomedical subjects

J Z Nowak

Publications and source records attributed to J Z Nowak.

At least 127 records · Page 7Linked to original sources
PubMed1975

Histamine content and synthesis in central and pheripheral nerve structures during stress.

Histamine content and histidine decarboxylase activity in cortex and hypothalamus, together with histamine content in peripheral nervous structures were examined in normal and electrically stressed guinea-pigs. A significant increase in histidine decarboxylase activity in hypothalamus and cortex together with concomitant decrease in histamine content in hypothalamus have been found. Electric shock causes also a decrease in histamine content in spinal cord, spinal ganglia, dorsal roots and sensory nerve. The function of histamine in nervous system is discussed.

Animals↗
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Regulation of melatonin and dopamine biosynthesis in chick retina: the role of GABA.

Melatonin biosynthesis in chick retina occurs as a circadian rhythm. Biosynthesis of the neurohormone is highest at night in darkness, and is suppressed by light. The role of gamma-aminobutyric acid (GABA) in the nocturnal regulation of melatonin synthesis was examined. Systemic or intravitreal administration of muscimol, a GABA-A receptor agonist, to light-exposed chicks at the beginning of the dark phase of the light/dark cycle increased retinal melatonin levels and the activity of serotonin N-acetyltransferase (NAT), a key regulatory enzyme of the melatonin biosynthetic pathway. Baclofen, a GABA-B receptor agonist, also increased NAT activity of light-exposed retinas, but muscimol was approximately 40-fold more potent than baclofen. Effects of both muscimol and baclofen on NAT activity were inhibited by GABA-A antagonists, bicuculline and picrotoxin, and the effect of baclofen was unaffected by the GABA-B selective antagonist, CGP 35348. Thus, activation of GABA-A receptors appears to be associated with increased melatonin biosynthesis. The GABA-uptake inhibitor, nipecotic acid, and the GABA-transaminase inhibitor, aminooxyacetic acid, also increased NAT activity of light-exposed retinas. The high levels of NAT activity associated with exposure to darkness were unaffected by either muscimol or baclofen, but picrotoxin and bicuculline significantly inhibited retinal NAT activity in darkness. The rate of dopamine synthesis, estimated from in situ tyrosine hydroxylase activity, was higher in light-exposed retinas than in darkness. Muscimol inhibited dopamine synthesis in light, and picrotoxin stimulated dopamine synthesis in darkness. The stimulation of melatonin synthesis by muscimol in light-exposed retinas appears to be related to inhibition of retinal dopamine neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

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Serotonin N-acetyltransferase activity in chicken retina: in vivo effects of phosphodiesterase inhibitors, forskolin, and drugs affecting dopamine receptors.

A role of D2-dopaminergic neurotransmission in the regulation of melatonin biosynthesis in retina was studied in vivo in chickens. The nighttime rise in serotonin N-acetyltransferase (NAT)--the penultimate and key regulatory melatonin-synthesizing enzyme--was potently inhibited by both acute light exposure and agonists of dopamine D2-receptor (quinpirole, bromocriptine, and apomorphine). Spiroperidol, a selective dopamine D2-receptor blocker, increased the enzyme activity in light-exposed chickens, but had no effect in animals kept in darkness. Inhibitors of cyclic nucleotide phosphodiesterase, aminophylline, and 3-isobutyl-1-methylxanthine given peripherally, along with a direct adenylate cyclase activator forskolin injected directly into the eye, mimicked the action of darkness, and markedly enhanced the retinal NAT activity when administered to animals maintained in an illuminated environment. Dopamine D2-receptor agonists had no effect on aminophylline-stimulated enzyme activity, whereas spiroperidol enhanced it. Forskolin-driven NAT activity was suppressed by quinpirole. Spiroperidol and aminophylline given alone at different times of day under light conditions stimulated NAT activity, and their effects were mainly additive when given in combination. SCH 23390, a selective D1-dopamine receptor antagonist, did not affect the rise in NAT activity of chicken retina produced by either darkness or by aminophylline. The results provide further evidence that dopamine, acting via D2-receptors, mediates the inhibitory effects of light on the cyclic AMP-dependent dark-evoked induction of NAT activity in chicken retina.

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Effects of near-ultraviolet (UV-A) light on melatonin biosynthesis in vertebrate pineal gland.

The effects of near-ultraviolet (UV-A) irradiation on nocturnal activity of serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthesis) in the pineal gland of the rat and chick were investigated. Exposure of the animals to UV-A during the 4th or 5th hour of the dark phase of the 12:12 h light-dark (LD) cycle suppressed the night-driven NAT activity in a time-dependent manner, the effects being generally more pronounced in rats than in chicks. The UV-A-evoked suppression of the nocturnal NAT activity was completely restored within 2 h (chicks) or 3 h (rats) in animals which, after irradiation, were returned to darkness. When a short UV-A pulse was applied to the animals after midnight, it induced a decrease in the enzyme activity in both species; yet, the effect was readily reversible only in chicks. The results presented here, as well as other data, demonstrate that UV-A light is a powerful signal affecting the pineal melatonin-generating system both in mammals and avians, and that the involved mechanisms may differ in the tested species.

Animals↗
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Effects of calcium ions and substances affecting Ca2+ -related mechanisms on histamine-evoked stimulation of cyclic AMP formation in chick pineal gland.

In avian central nervous system (CNS), and particularly in the pineal gland, histamine (HA) potently stimulates synthesis of cyclic AMP in intact tissue, and only weakly affects adenylyl cyclase activity in membrane preparation. In this work, we focussed on calcium (Ca2+) as a possible link in the mechanism through which HA affects cyclic AMP generation in the chick pineal. The problem was studied in two sets of experiments where the action of HA on the pineal cyclic AMP was tested: (1) in the incubation medium containing various compounds influencing Ca2+ influx and/or Ca2+ intracellular concentration/action (Ca2+ -ionophore calcimycin, Ca2+ -channel agonist Bay-K 8644, Ca2+ -channels blockers: diltiazem, verapamil, nifedipine and omega-conotoxin-GVIA, CaCl2, EGTA in the absence of CaCl2 in the incubation medium, as well as calmodulin inhibitors: calmidazolium and W-7), and (2) in a CaCl2-free incubation medium yet containing different concentrations of BaCl2, CdCl2, CoCl2, MgCl2, and NiSO4. The results of the first series were mostly negative; an exception was the inhibiton of the HA-evoked cyclic AMP formation observed in the presence of 5.2 and 10.4 mM CaCl2 In the second series of experiments, divalent cations (however with the exception of Mg2+, which was inactive at concentrations up to 15.6 mM) inhibited the HA-evoked cyclic AMP production, with the following rank order of potency: Cd2+ >> Co2+ >> Ni2+ > Ba2+. The inhibitory effect of CdCl2 was prevented by nifedipine. Taken together, the present data suggest that intracellular Ca2+ -related mechanisms are not of major importance in the HA action on cyclic AMP synthesis in the chick pineal. It could be suspected that the inhibition of the HA-driven cyclic AMP formation by high concentrations of Ca2+, and other divalent cations, probably resulted from their direct inhibitory interaction with the catalytic site of the pineal adenylyl cyclase.

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PubMedDate not supplied

Melatonin: from biochemistry to therapeutic applications.

Melatonin (N-acetyl-5-methoxytryptamine) is an evolutionary highly conserved molecule that plays an important role in conveying the clock and calendar information to all living organisms, including man. The hormone is synthesized mainly by the pineal gland, and, to a lesser extent, by extrapineal tissues--such as the retina, Harderian gland, and gastrointestinal tract. The melatonin-generating system is characterized by three basic features: (1) photosensitivity, (2) diurnal (or circadian) rhythmicity (with highest levels of the hormone production occurring at night in darkness), and (3) age-related decrease in its activity. This review surveys data on the regulation of rhythmic melatonin biosynthesis by an array of factors, such as circadian pacemaker, light, neurotransmitters, second and third messenger molecules. Recent developments in the field of melatonin receptors are also presented. Finally, physiological and therapeutic properties of melatonin, with a special emphasis given to possible applications of this compound in the treatment of circadian rhythm sleep disorders, are discussed.

Aging↗
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Stimulatory effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on cyclic AMP formation in the hypothalamus and cerebral cortex of four avians and rat.

PACAP38 and PACAP27, tested at 0.0001-1 microM, potently stimulated synthesis of cyclic AMP in the hypothalamus and cerebral cortex of chicks; the effects of vasoactive intestinal polypeptide (VIP) in the two brain regions were much weaker, reaching statistical significance only at 3 microM concentration. This characteristics suggests the existence in the bird's brain of adenylyl cyclase-linked PAC1 receptors. PACAP27 (0.001-1 microM) concentration-dependently stimulated cyclic AMP production in the hypothalamus and cerebral cortex of three other birds: duck, goose and turkey; the effects were, however, somewhat lower than those in chicks, but comparable to those found in rats. These data demonstrate PACAP to be capable of potently stimulating cyclic AMP generating system in the avian central nervous system.

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Effects of neuropeptides of the secretin/VIP/PACAP family on cyclic AMP formation in the chick hypothalamus and cerebral cortex.

Six neuropeptides: short and long form of the pituitary adenylate cyclase activating polypeptide (PACAP), i.e. PACAP27 and PACAP38, vasoactive intestinal peptide (VIP), peptide histidine-isoleucine (PHI), secretin and glucagon, members of the secretin/VIP/PACAP superfamily ofpolypeptides, were tested for their ability to stimulate cyclic AMP formation in [3H]adenine-prelabeled slices of the chick hypothalamus and cerebral cortex. Of the tested peptides, only PACAP evoked pronounced and significant responses in the two analyzed brain structures. Although magnitude of the responses varied in different experiments, the effects of both forms of PACAP were usually larger in the cerebral cortex than in the hypothalamus. Glucagon, PHI (both used at concentrations 0.01-1 microM) and VIP (0.1-3 microM) induced concentration-dependent yet comparatively small effects that did not reach statistical significance, while secretin (0.1-3 microM) had no effect.

Amino Acid Sequence↗
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Effect of glucocorticoid dexamethasone on cyclic AMP formation stimulated by pituitary adenylate cyclase-activating polypeptide (PACAP) in the cerebral cortex and hypothalamus of chick.

In this study we tested in chicks the effects of acute and chronic in vivo treatment with a glucocorticoid dexamethasone (4 mg/kg, i.p.) on PACAP-stimulated cyclic AMP formation in [3H]adenine-prelabeled slices of the hypothalamus and cerebral cortex. PACAP (1-100 nM) concentration-dependently stimulated cyclic AMP formation in both brain regions of chick. In acute experiments, dexamethasone (single dose)-injected chicks were killed after 2, 24 and 48 h; while in chronic experiment the glucocorticoid was given once daily for 12 days and the animals were killed 48 h after the last injection. The ability of PACAP to stimulate cyclic AMP formation in the hypothalamus and cerebral cortex was similar in vehicle-treated (control) and dexamethasone-treated animals, with the exception of the nucleotide response to 100 nM of the peptide in both brain regions, which was significantly larger in the group of chicks killed 48 h after the administration of the single steroid dose.

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) activate protein kinase C in chick cerebral cortex.

Pituitary adenylate cyclase-activating polypeptide (PACAP38) and vasoactive intestinal peptide (VIP) were tested for their ability to influence protein kinase C (PKC) activity in the chick cerebral cortical slices. Thirty minutes incubation of the chick tissue with PACAP38 (0.1-1 microM) or VIP (0.3-3 microM) produced significant and concentration-dependent changes in PKC activity. Both peptides enhanced the enzyme activity in cell membrane preparation, and decreased it in cytosol preparation obtained from cerebral cortical slices. These changes in PKC activity suggest that PACAP and VIP are capable of activating this enzyme in cerebral cortex of chick.

Animals↗
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The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina.

The in vivo effects of GABA-ergic drugs on the activity of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM)-stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina.

Acetylserotonin O-Methyltransferase↗
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The influence of histamine on metabolism of dopamine and serotonin in the rat striatum.

The influence of histamine on metabolism of dopamine and serotonin in the rat striatum. Acta Physiol. Pol., 1977, 28 (2): 101--105. Histamine-2HC1 (Hi) given in a dose of 500 micron g did not change DA level in the striatum but HVA was increased by approx. 50%. The Hi-induced rise of HVA level was prevented in animals pretreated with an antihistaminic drug--mepyramine. The pretreatment of rats with atropine reduced significantly the Hi-induced rise of HVA concentration. Hi did not significantly influence 5-HT content in the striatum while the level of 5-HIAA was simultaneously increased by 15%. It is concluded that Hi-induced elevation of HVA content is not a direct effect of Hi on dopaminergic neurons but the Hi action is exerted indirectly through cholinergic system. The increase of serotoninergic activity is probably a consequence of an increased activity of dopaminergic neurons in the striatum.

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Light modulates dopamine-regulated Walsh inhibitor activity and dopamine-dependent cyclic AMP accumulation in the rabbit retina.

The effect of various dopaminergic agents and related drugs on the activity of the heat-stable inhibitor of cyclic AMP (cAMP)-dependent protein kinase (Walsh inhibitor) and on cAMP accumulation was studied in retinas of light- and dark-adapted rabbits. Both in dark- and light-adapted rabbits low doses of apomorphine increased the retinal Walsh inhibitor activity; high doses of the drug decreased the Walsh inhibitor activity in dark-adapted rabbits, but were without effect in light-adapted animals. S-Sulpiride antagonized the effect of low doses of apomorphine on the Walsh inhibitor activity, and, in contrast to haloperidol (which was effective), did not affect the action of a high apomorphine dose. Selective agonists of dopamine (DA) D2-receptor, quinpirole and bromocriptine, increased the retinal Walsh inhibitor activity in both light- and dark-adapted animals, a selective D1-agonist, SKF 38393, decreased the inhibitor activity in dark- and did not significantly modify it in light-adapted animals. In in vitro experiments, carried out in the presence of theophylline, DA and apomorphine increased cAMP accumulation in pieces of the rabbit retina through activation of D1-receptors. The action of DA, apomorphine, and SKF 38393, was significantly stronger in retinas of dark- than of light-adapted animals. Forskolin stimulated cAMP accumulation in a concentration-dependent manner, producing at 100 microM increases of cAMP levels by approximately 5-fold. DA and SKF 38393 did not significantly modulate the action of 10 microM forskolin, whereas apomorphine slightly decreased the forskolin effect. Of the two selective D2-receptor agonists, bromocriptine slightly decreased, and quinpirole had no effect on the forskolin action. The characteristics of the specific binding of [3H]spiroperidol were essentially the same in the retinas of dark- and light-adapted rabbits. Our data suggest that in light-adapted animals the D1-receptors, or the effector mechanisms for regulation of the Walsh inhibitor activity, may be desensitized. Our results suggest also that in the rabbit retina there are probably no D2-receptors coupled negatively to adenylate cyclase, although a pharmacologically similar class of DA receptors seems to be involved in regulation of the Walsh inhibitor activity (in a way independent on environmental lighting).

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Histamine in the rat brain: effect of acute and chronic treatment with tricyclic antidepressants and H1-antihistaminics.

Prolonged (for two weeks), but not acute, intensive treatment with tricyclic antidepressant drugs (amitriptyline, AMI; doxepine, DOX; imipramine, IMI) and H1-antihistaminics (chloropyramine, CPYR; diphenhydramine, DPHA; promethazine, PMZ; tripelenamine, TPA) decreased histamine (HI) level in rat brain, especially in the cerebral cortex. These drugs did not modify L-histidine decarboxylase activity in any analyzed brain structure, except chronically given AMI and IMI which significantly increased the enzyme activity. None of the tested compounds, administered both acutely or chronically, affected the activity of HI-methyltransferase, as well as HI level in the heart. Under in vitro conditions, all antidepressants, PMZ and CPYR, but not DPHA or TPA, only at high concentrations (10(-3) or 3 X 10(-3M) released HI from both pleural and PMZ did not modulate the pleural mast cells HI-releasing profile of both DOX or DPHA. Chronic treatment with the antidepressants and the H1-antihistaminics decreased slightly but not significantly HI contents in the brains of L-histidine-treated rats. It is suggested that the decrease in the brain HI levels induced by chronic administration of both tricyclic antidepressants and H1-antihistaminics is, most probably, a consequence of HI release from central histaminergic nerve terminals; this release could result from the drug-produced persistent blockade of central H1- and/or H3- (i.e. HI auto-receptors)receptors.

Animals↗