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Biomedical subjects

J Z Nowak

Publications and source records attributed to J Z Nowak.

At least 73 records · Page 4Linked to original sources
PubMed1990

Retinal dopamine D1 and D2 receptors: characterization by binding or pharmacological studies and physiological functions.

1. In the retinal inner nuclear layer of the majority of species, a dopaminergic neuronal network has been visualized in either amacrine cells or the so-called interplexiform cells. 2. Binding studies of retinal dopamine receptors have revealed the existence of both D1- as well D2-subtypes. The D1-subtype was characterized by labeled SCH 23390 (Kd ranging from 0.175 to 1.6 nM and Bmax from 16 to 482 fmol/mg protein) and the D2-subtype by labelled spiroperidol (Kd ranging from 0.087 to 1.35 nM and Bmax from 12 to 1500 fmol/mg protein) and more selectively by iodosulpiride (Kd 0.6 nM and Bmax 82 fmol/mg protein) or methylspiperone (Kd 0.14 nM and Bmax 223 fmol/mg protein). 3. Retinal dopamine receptors have been also shown to be positively coupled with adenylate cyclase activity in most species, arguing for the existence of D1-subtype, whereas in some others (lower vertebrates and rats), a negative coupling (D2-subtype) has been also detected in peculiar pharmacological conditions implying various combinations of dopamine or a D2-agonist with a D1-antagonist or a D2-antagonist in the absence or presence of forskolin. 4. A subpopulation of autoreceptors of D2-subtype (probably not coupled to adenylate cyclase) also seems to be involved in the modulation of retinal dopamine synthesis and/or release. 5. Light/darkness conditions can affect the sensitivity of retinal dopamine D1 and/or D2-receptors, as studied in binding or pharmacological experiments (cAMP levels, dopamine synthesis, metabolism and release). 6. Visual function(s) of retinal dopamine receptors were connected with the regulation of electrical activity and communication (through gap junctions) between horizontal cells mediated by D1 and D2 receptor stimulation. Movements of photoreceptor cells and migration of melanin granules in retinal pigment epithelial cells as well as synthesis of melatonin in photoreceptors were on the other hand mediated by the stimulation of D2-receptors. 7. Other physiological functions of dopamine D1-receptors respectively in rabbit and in embryonic avian retina would imply the modulation of acetylcholine release and the inhibition of neuronal growth cones.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Bidirectional regulation of cAMP generating system by dopamine-D1 and D2-receptors in the rat retina.

Accumulation or inhibition of cAMP formation in response to dopamine or dopamine related drugs in the absence or in the presence of forskolin and/or IBMX was investigated in isolated rat retina. While the existence of D1-receptors (positively coupled with adenylate cyclase) was confirmed, D2-receptors (negatively coupled to adenylate cyclase) were also revealed by using a selective D1-antagonist (SCH 23390), a D2-agonist (LY 171555) or two D2-antagonists (S-sulpiride, spiroperidol). These results indicate that rat retina may be used for the study of both types of dopamine-receptors.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Histamine in the retina: recent progress and perspectives.

This article presents some new findings, and shortly surveys recently published data, on histamine (HA) in the retina of several vertebrates (carp, hen, rabbit, rat, guinea pig, cow, man). Analysis of various parameters (HA level, activity of histidine decarboxylase and HA-methyltransferase, release and uptake of HA, 3H-mepyramine binding, effect of HA on cAMP accumulation, diurnal variations) in vertebrate retina and brain shows that histaminergic systems in these sites are comparable, although some species-dependent differences have been observed. Interestingly, exposure of dark-adapted rabbits to light affects several histaminergic parameters selectively, i.e. in the retina and not in the brain. The reviewed data suggest that in retinas of at least some vertebrates HA may be a physiologically important amine.

Animals↗
PubMed1990

Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites.

Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors.

Animals↗
PubMed1989

Dopamine in the rabbit retina and striatum: diurnal rhythm and effect of light stimulation.

In rabbits, dopamine levels in the retina, but not in the caudate nucleus, showed clear diurnal rhythm, with high values seen in the light phase. Thirty min exposition of dark-adapted rabbits to day-light produced no changes in dopamine levels in the retina. In rabbits treated with alpha-methyl-p-tyrosine, the same light exposition decreased the retinal amine level by 18%, while stimulation with intensive, flickering light significantly decreased the retinal dopamine content by 36%. Experiments performed at noon and midnight, under light or dark conditions, showed the retinal dopamine levels to be very similar in groups kept either at light or dark, irrespective of the time of the day, although in animals deprived of light the amine levels were clearly lower than in those exposed to light, both at noon and midnight. Under all experimental conditions there were no significant changes in dopamine level and utilization in the caudate nucleus. The isolated and superfused retina (preloaded with [3H]-dopamine), when stimulated with flashes of white light (2 Hz, 10 min), released [3H]-radioactivity in a Ca2+-dependent manner. It is concluded that in rabbits, light enhances dopamine levels and utilization selectively in the retina, and the observed diurnal changes in the amine metabolism are dependent on the presence or absence of light, and not on the time of the day. The proposed physiological role(s) of the retinal dopaminergic mechanisms is discussed.

Animals↗
PubMed1989

Histamine-mediated regulation of cAMP levels and inositol phosphate metabolism in isolated rabbit retina.

In pieces of the rabbit retina, histamine (HI) had no significant effect on cAMP accumulation; however, HI inhibited forskolin-evoked accumulation of the nucleotide. Mepyramine (H1-antagonist) was without effect, while cimetidine (H2-antagonist) antagonized the HI action. Dimaprit (H2-agonist) mimicked the HI action, however its action was not significantly affected by H2-antagonists. Since phosphodiesterase (PDE) inhibitors prevented the HI action it is suggested that HI-induced inhibition of the forskolin effect results from HI-induced activation of cAMP breakdown. The muscarinic agonist carbachol, and to a lesser extent HI, both increased [3H]inositol incorporation and intensified accumulation of [3H]inositol phosphates in the rabbit retina.

Animals↗
PubMed1988

Circadian rhythm of histamine metabolism in the rabbit central nervous system (CNS): analysis of brain and ocular structures.

The circadian rhythm of the level of histamine (HI) and histidine decarboxylase (HD) and histamine-methyltransferase (HMT) activity in 6 brain and 5 ocular structures of the rabbit was studied. Clear circadian variations of the histaminergic parameters in two brain (hypothalamus and lateral geniculate body) and two ocular (retina and iris-ciliary body) tissues were found. It is suggested that HI in some brain and ocular structures may be functionally involved in activity that depends on circadian rhythm.

Animals↗
PubMed1988

Histamine dependent cyclic AMP generating system in rabbit CNS: interaction with neuroregulators and forskolin.

Histamine (HI) potently stimulated, through H2-receptors, cAMP accumulation in rabbit cerebral cortical slices but not in retinal pieces. The action of HI in the cerebral cortex was not significantly affected by dopamine, serotonin, melatonin and GABA-ergic drugs. Forskolin markedly stimulated cAMP accumulation both in the cerebral cortex and retina. There was a synergistic interaction between HI and forskolin in the cerebral cortex, whereas in the retina HI decreased the forskolin-activated cAMP accumulation.

Animals↗
PubMed1987

Histamine dependent cAMP generating system in rabbit CNS: interaction with various neuroregulators.

Histamine (HI) potently stimulated, through H2-receptors, cAMP accumulation in slices of the rabbit cerebral cortex (EC50: 15 microM; maximum stimulation: 300-450% of the basal level). Combination of L-noradrenaline or L-adrenaline and adenosine with HI showed synergistic and additive effects, respectively. Carbachol, arecoline and pilocarpine had no effect, while oxotremorine and tremorine increased and decreased the HI response when used at low or high concentrations, respectively.

Adenosine↗
PubMed1987

Histamine in the human eye.

Various ocular structures (iris, ciliary body, choroid, retina, sclera, optic nerve) were enucleated from human eyes suffering endophthalmitis, perforative wounds of cornea and/or sclera, or uncontrolled glaucoma, and were tested for their histamine content. All of the tested tissues contained histamine with the highest and the lowest values always found in the uvea and retina, respectively. The eyes of the 'endophthalmitis' group showed histamine levels 5-10 times higher than amine levels found in the traumatized eyes, whereas the eyes of the 'glaucoma' group were characterized by intermediate amine contents.

Adolescent↗
PubMed1986

Brain histamine metabolism in transmissible spongiform encephalopathy (scrapie).

The histamine (Hi) content and the activity of L-histidine decarboxylase (HD) in brains of scrapie infected hamsters were measured. No significant changes in Hi levels in particular brain areas were found when compared to controls. Decreased activity of HD was found in hypothalamus (p less than 0.02). Increased activity of the enzyme was observed in "rest of brain", which consisted mainly of thalamus and striatum (p less than 0.05).

Animals↗
PubMed1986

3H-mepyramine binding and histamine-stimulated cAMP accumulation in mammalian retina.

The specific binding of different amounts of 3H-mepyramine to the bovine retina revealed a quasi-hyperbolic curve which approached saturation at 3H-ligand concentration over 9-12 nM. Scatchard analysis of the binding data showed two binding sites with KD values of 0.76 nM and 7.3 nM and Bmax of 49.3 and 194.6 fmole/mg protein, respectively. In the guinea-pig brain 3H-mepyramine bound to a single population of binding sites with KD value of 1.6 nM and Bmax of 291 fmole/mg protein. Various H1-antihistamines were potent competitors of the 3H-mepyramine binding: there was a big difference in potency of d- and 1-chlorpheniramine in both membrane preparations. In the rabbit retina slices histamine, in contrast to dopamine, weakly stimulated cAMP accumulation. The data suggest that the mammalian retina may possess histamine receptors.

Aminopyridines↗