Search PubMed⌕ Search

Biomedical subjects

G Fried

Publications and source records attributed to G Fried.

At least 91 records · Page 5Linked to original sources
PubMed1988

Differential distribution of 5-hydroxytryptamine and substance P in synaptosomal vesicles of rat ventral spinal cord.

The subcellular distribution of 5-hydroxytryptamine (5-HT) and substance P (SP) was investigated in rat ventral spinal cord using differential and density gradient centrifugation. 5-HT was determined by high performance liquid chromatography (HPLC) and SP by radioimmunoassay (RIA). Both substances were found to be stored within synaptosomes at high densities. After partial lysis of the synaptosomes, 5-HT was also recovered in low density fractions, while substance P was found also in a fraction of intermediate density. The results indicate that within synaptosomes from ventral spinal cord, most of the 5-HT is stored in small synaptic vesicles, while SP is only stored in large synaptic vesicles. A minor part of the 5-HT may in addition also be stored in large vesicles, as previously suggested by ultrastructural studies.

Animals↗
PubMed1988

Postnatal development of catecholamines and response to hypoxia in adrenals and paraganglia of rabbits.

The postnatal development of catecholamine levels in adrenals and paraganglia in newborn rabbits has been analyzed. At birth, the dominant catecholamine was noradrenaline, contributing 66% of the total catecholamine pool at day 1, 55% of which came from the paraganglia. There was a rapid postnatal increase of adrenaline, which constituted 67% of the total catecholamines at day 6 and 97% in the adult. After hypoxia at day 1, the noradrenaline levels decreased in paraganglia but not in adrenals, while adrenaline levels did not significantly change in either organ.

Adrenal Glands↗
PubMed1988

Immunohistochemical evidence for the existence of a dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32) in brown adipose tissue of pigs.

The indirect immunofluorescence technique was used to study the cellular localization of DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein, in brown adipose tissue of newborn piglets. Clusters of strongly DARPP-32-immunoreactive cells were found in brown adipose tissue from the interscapular area and around lymph nodes close to the kidneys, adrenal glands, descending aorta, and great veins in the neck. The DARPP-32-immunoreactive cells contained multilocular lipid droplets, had round, centrally located nuclei, and were polygonal in shape, thus possessing characteristics and location sites typical for brown fat cells. The results indicate that brown adipose tissue from the newborn pig contains DARPP-32, an intracellular third messenger for dopamine. Together with recent functional data, these results strongly suggest that dopaminergic D1 mechanisms--i.e., activation of adenylate cyclase and formation of cyclic AMP--may be involved in cold-induced, nonshivering, and/or diet-induced thermogenesis.

Adipose Tissue, Brown↗
PubMed1987

Neuropeptide Y and noradrenaline mechanisms in relation to reserpine induced impairment of sympathetic neurotransmission in the cat spleen.

The mechanisms underlying the reserpine-induced impairment of the functional responses to sympathetic nerve stimulation and output of noradrenaline (NA) and neuropeptide Y (NPY)-like immunoreactivity (-LI) were studied using the isolated blood-perfused cat spleen. Splenic nerve stimulation (10 Hz for 2 min) during control conditions caused perfusion-pressure increase, volume reduction and an increased output of NA and NPY-LI. After administration of phenoxybenzamine, the nerve stimulation-induced perfusion-pressure increase was almost abolished, the volume reduction inhibited and the output of NPY-LI enhanced. After subsequent addition of propranolol, a clear-cut increase in perfusion pressure upon nerve stimulation reappeared. Local infusion of NPY caused a potent, long-lasting, adrenoceptor-resistant increase in perfusion pressure and a relatively smaller volume reduction of the spleen. Twenty-four hours after reserpine pretreatment (1 mg kg-1 i.v.), which depleted the splenic content of NA greater than 95% and NPY-LI by about 50%, the functional responses upon nerve stimulation were markedly reduced. Preganglionic denervation or pretreatment with the ganglionic-blocking agent chlorisondamine did not influence the NA depletion after reserpine treatment. A considerable, adrenoceptor antagonist-resistant, long-lasting functional response as well as a markedly enhanced output of NPY-LI then occurred upon nerve stimulation. In conclusion, reserpine treatment combined with interruption of preganglionic impulse flow reveals non-adrenergic, nerve stimulation evoked splenic functional responses which could be mediated by release of a cotransmitter peptide like NPY.

Adrenergic alpha-Antagonists↗
PubMed1986

Neuropeptide Y, enkephalin and noradrenaline coexist in sympathetic neurons innervating the bovine spleen. Biochemical and immunohistochemical evidence.

The subcellular distribution of noradrenaline (NA), neuropeptide Y (NPY), Met- and Leu-enkephalin (ENK), substance P (SP), somatostatin (SOM), and vasoactive intestinal polypeptide (VIP) was investigated in homogenates of bovine splenic nerve. The distribution of noradrenergic peptide-containing nerves in the bovine celiac ganglion, splenic nerve and terminal areas in spleen was studied by indirect immunofluorescence histochemistry using antisera to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), NPY, enkephalin peptides, SP, SOM, VIP, and peptide HI (PHI). After density gradient centrifugation, high levels of NPY- and ENK-like immunoreactivity (LI) were found in high-density gradient fractions, coinciding with the main NA peak. SP, SOM and VIP were found in fractions with a lower density, VIP being also enriched in a heavy fraction; the latter three peptides were present in low concentrations. Immunohistochemistry revealed that staining for NPY-LI and ENK-LI partly overlapped that for TH and DBH in celiac ganglia, splenic nerve axons and terminal areas of spleen. Almost all principal ganglion cells were TH- and DBH-immunoreactive. Many were also NPY-immunoreactive, whereas a smaller number were ENK-positive. In the celiac ganglion patches of dense SP-positive networks and some VIP/PHI- and ENK-immunoreactive fibers were seen around cell bodies. The results indicate that NPY and ENK are stored with NA in large dense-cored vesicles in unmyelinated axons of bovine splenic nerve. SP, SOM and VIP appear in different organelles in axon populations separate from sympathetic noradrenergic nerves.

Adrenergic Fibers↗
PubMed1986

Neuropeptide Y and noradrenaline in human uterus and myometrium during normal and pre-eclamptic pregnancy.

The myometrial levels of noradrenaline (NA) and neuropeptide Y (NPY), a recently discovered neuropeptide that coexists with NA in many sympathetic nerves, have been measured by immunohistochemistry and biochemistry in normal and pre-eclamptic pregnancy and compared with non-pregnant controls. In the non-pregnant uterus there were high levels of NA and NPY and a rich presence of NA/NPY nerves in the myometrium and around blood vessels. In pregnancy both substances were significantly lower as compared with non-pregnant women. Five patients with pre-eclampsia had levels of NA/NPY that were less markedly reduced than in normal pregnant women. The results show that NA and NPY coexist also in human uterine nerves, and that both decrease significantly during pregnancy. Since both substances are vasoactive, the observed reduction might be of physiological importance for normal pregnancy.

Female↗
PubMed1986

Co-release of neuropeptide Y and catecholamines upon adrenal activation in the cat.

The release of neuropeptide Y (NPY)-like immunoreactivity (-LI) in relation to catecholamines from the cat adrenal was studied in anaesthetized animals. Abdominal surgery increased plasma levels of NPY-LI from 65 +/- 6 to 149 +/- 26 pmol l-1. A positive veno-arterial concentration gradient over the adrenal gland was found for both NPY-LI, adrenaline (Adr) and noradrenaline (NA) during basal conditions. Asphyxia for 2 min increased the output of both NPY-LI and catecholamines from the adrenal. Electrical stimulation of the splanchnic nerve caused a marked increase in adrenal output of NPY-LI and catecholamines. The adrenal content of NPY-LI, as well as the release of NPY-LI from the adrenal, was at least 1000-fold lower on a molar basis than that of catecholamines. The concentration of NPY-LI in the adrenal vein upon splanchnic nerve stimulation was in the nM range. Reversed-phase HPLC characterization revealed that NPY-LI in the adrenal, and in the adrenal venous plasma collected during splanchnic nerve stimulation, was closely related to synthetic porcine NPY. Stimulation with bursts of 20 Hz for 1 S with 10 s intervals for 2 min caused a four-fold higher output of NPY-LI and Adr compared to a continuous stimulation with 2 Hz, giving the same number of impulses. The NA output, however, was only slightly increased by burst stimulation. Guanethidine did not reduce the adrenal output of NPY-LI or catecholamines induced by splanchnic nerve stimulation, while the release was abolished by chlorisondamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1985

Neuropeptide Y (NPY)-like immunoreactivity in guinea pig uterus is reduced during pregnancy in parallel with noradrenergic nerves.

Neuropeptide Y (NPY) is a recently discovered neuropeptide with vasoconstrictor effects when given in vivo. It occurs in many sympathetic neurons, where it appears to coexist with noradrenaline (NA). It is wellknown that profound changes in the levels of uterine NA occur in many species during pregnancy. Therefore we have investigated the distribution of catecholamine neurons and NPY by immunohistochemistry in the pregnant and nonpregnant guinea pig uterus. In the virgin uterus NPY-like immunoreactivity was present in nerve fibres and terminals in the smooth muscle layers of the uterine horns and around blood vessels. The distribution of NPY fibres was very similar to that of noradrenergic nerves visualized with antibodies against the catecholamine synthesizing enzyme tyrosine hydroxylase (TH). In the pregnant uterus, NPY- and TH-like immunoreactivity disappeared almost completely. In the cervix, a slight decrease of immunoreactivity was observed, whereas in the ovaries no changes were noted between the pregnant and nonpregnant condition. The results indicate that NPY and catecholamines coexists in the adrenergic neurons of the guinea pig uterus, cervix and ovary and that they vary together in the myometrium during pregnancy. We suggest that NPY may be of functional importance for the pregnant uterus.

Adrenergic Fibers↗
PubMed1985

Reduced uptake of noradrenaline into storage vesicles from the pregnant uterus.

A noradrenaline (NA) storage vesicle fraction was isolated from the uteri of virgin as well as pregnant guinea-pigs. The uptake of 3H-NA into respective vesicle fractions was compared. Total uptake of 3H-NA in the presence of Mg2+ (2.5mM) and ATP (2.5 mM) at 30 degrees C after 20 min was 6.0 +/- 1.4 pmol . mg-1 in uterus fractions from virgin guinea-pigs as compared to 1.87 +/- 0.41 pmol . mg-1 in uterus fractions from pregnant animals. When desipramine (5mM) was added in order to block neuronal uptake the corresponding figures were 4.75 +/- 0.92 and 0.51 +/- 0.18 pmol . mg-1, respectively. Thus in the presence of desipramine (5mM) uptake was reduced by 21.4% in fractions from virgin uteri but by 72.7% in fractions from pregnant uteri. Reserpine (0.1 microM) inhibited uptake of 3H-NA by 34% in fractions from virgin uteri and by 46% in fractions from pregnant uteri. Our results indicate a decreased amount of functional storage vesicles in uteri of guinea-pigs at term pregnancy and are consistent with the proposed degeneration of adrenergic nerves during pregnancy.

Adenosine Triphosphate↗
PubMed1985

Subcellular storage and axonal transport of neuropeptide Y (NPY) in relation to catecholamines in the cat.

The subcellular storage of neuropeptide Y-like immunoreactivity (NPY-LI) in peripheral sympathetic neurons and adrenal gland as well as its axonal transport in the sciatic nerve was studied in relation to catecholamines in the cat. In the subcellular fractions from different parts of sympathetic neurons, i.e. cell bodies (coeliac ganglia), axons (sciatic nerve) and terminals (spleen), the NPY-LI was found together with noradrenaline (NA) in heavy fractions assumed to contain large dense-cored vesicles. In addition, minor lighter fractions in the coeliac ganglion contained NPY-LI. The molar ratio between vesicular NA and NPY was high in the terminal regions (150 to 1) and much lower in axons and cell bodies (10 to 1), thus reflecting the different mechanisms of resupply for classical transmitter and peptide. In the adrenal gland the NPY-LI was mainly located in the catecholamine-storing chromaffin-granule fraction and also to a smaller extent in lighter fractions. Using reversed-phase HPLC, one molecular form of NPY-LI corresponding to porcine NPY was found in the coeliac ganglion, while the adrenal medulla also contained minor peaks with NPY-LI in addition to the main form, which co-eluted with porcine NPY. NA was stored both in light and heavy fractions in the spleen, while it was mainly found in heavier fractions in the sciatic nerve. In the coeliac ganglion, most of the noradrenaline was present in a non-particulate form. The anterograde transport rate for NPY-LI in the sciatic nerve was estimated to be about 9 mm h-1. A minor retrograde transport of NPY-LI was also detected. In conclusion, the present data suggest that NPY, a peptide with sympathoactive actions, is co-stored with NA in heavy fractions corresponding to large dense-cored vesicles, while light fractions with small dense-cored vesicles probably contain NA but not NPY-LI. The main resupply of NPY to terminals is, in contrast to NA, most likely by axonal transport, which implicates differences in the storage, turnover and release of these co-existing substances in the sympathoadrenal system.

Adrenal Medulla↗
PubMed1985

Evidence for differential localization of noradrenaline and neuropeptide Y in neuronal storage vesicles isolated from rat vas deferens.

Using the technique of homogenization and subsequent density gradient centrifugation combined with ultrastructural analysis, the subcellular localization of noradrenaline and neuropeptide Y (NPY) was studied in vas deferens of castrated male rats. Noradrenaline showed two peaks in the gradient: one major peak at low density and another at high density. Only one NPY peak was seen, which coincided with the high density peak of noradrenaline. Electron microscopic analysis revealed high proportions of small and large vesicles in the light and heavy fractions, respectively. The present results indicate a differential subcellular localization of noradrenaline and NPY in the noradrenergic nerve endings of vas deferens. Thus, small vesicles seem to contain only noradrenaline, whereas the large vesicles may contain both noradrenaline and NPY.

Animals↗
PubMed1984

Occurrence, storage and release of neurotensin-like immunoreactivity from the adrenal gland.

In the present study we have investigated the presence of radioimmunoassayable neurotensin-like immunoreactivity (NTLI) in extracts of adrenal glands from hen, guinea-pig, rat, cat, dog and man. In addition, gel filtration chromatography and studies on the storage site of NTLI, using subcellular fractionation techniques, were performed. Finally, NTLI release in relation to noradrenaline (NA) from cat adrenal glands upon splanchnic nerve activation was studied in vivo. In all species investigated except guinea-pig and man, the NTLI levels in the adrenal glands were higher than the levels in the heart (control tissue) but lower than in the ileum. Gel filtration of NTLI from cat adrenal glands revealed presence of roughly equal amounts of the whole neurotensin molecule, i.e. NT(1-13), and its main metabolite the N-terminal octapeptide NT(1-8), while in plasma from the adrenal vein almost exclusively NT(1-13) was revealed after electrical stimulation of the splanchnic nerve. The release of NTLI and NA upon splanchnic stimulation was antagonized by hexamethonium. Subcellular fractionation of cat adrenal glands indicated that NTLI was stored in a large subcellular organelle, co-migrating with chromaffin granules. We suggest that NT may be a new adrenal gland hormone or transmitter, possibly co-stored with NA in chromaffin cells. However, at the present stage it cannot be distinguished whether NT exerts its actions locally within the adrenal gland or after release into the systemic circulation.

Adrenal Glands↗
PubMed1982

Origin of adenosine released from rat vas deferens by nerve stimulation.

After labelling of vasa deferentia from intact rats with [3H] adenine there was a spontaneous outflow of labelled purines, mainly as adenosine inosine and hypoxanthine. There as a spontaneous outflow of endogenous adenosine and inosine amounting to 6 and 2 pmol/min from a single vas. The uptake inhibitor dipyridamole increased the rate of outflow to 27 and 28 pmol/min. respectively. Transmural nerve stimulation of vasa from intact and castrated rats increased the rate of purine release but with a different time course than for the release of [3H] noradrenaline ([3H]NA). Phentolamine (3 microM) increased [3H] NA release, suggesting the presence of presynaptic alpha-adrenoceptors in castrated vasa, but almost abolished purine release. Adenosine (1 microM) decreased [3H] NA release without affecting [14C] purine overflow. Dipyridamole (1 microM) had a opposite effect. The inhibitory effect of adenosine on noradrenaline release was similar in intact and castrated vasa. In the subcellular distribution studies ATP was detected in the small, dense-cored vesicle fraction, but the ratio ATP:NA was only 1.20-1.60. Labelling of the vesicle fraction by [3H] adenine was usually found, but the degree of labelling was small. The results indicate that endogenous adenosine is released from rat vas deferens in amounts that may be sufficient to cause pre- and postjunctional effects. In particular the amounts of ATP released together with NA are suggested to be quantitatively insignificant.

Adenosine↗
PubMed1982

Cellular and subcellular localization of protein I in the peripheral nervous system.

The cellular and subcellular distribution of protein I, a major brain phosphoprotein, has been studied in the peripheral nervous system. The levels of protein I in various peripheral nerves and innervated peripheral tissues were determined by radioimmunoassay and radioimmunolabeling of polyacrylamide gels. The results indicated tha protein I is present throughout the peripheral nervous system. Denervation studies of adrenal medulla and iris suggested that the protein I contained in peripheral tissues is localized to the neuronal elements innervating those tissues. Protein I was found to be enriched in neurotransmitter vesicle fractions of peripheral nervous tissue. Moreover, protein I appeared to be transported from cell bodies to axons terminals at least partly in association with neurotransmitter vesicles.

Adrenal Glands↗