Moderate cooling depresses the accumulation and the release of newly synthesized catecholamines in isolated canine saphenous veins

Summary Moderate cooling (from 37° to 24°C) depressed the formation of³H-dopamine and³H-norepinephrine from³H-tyrosine by isolated canine saphenous veins. Cooling reduced the evoked release ofnewly synthesized catecholamine to the same extent as tha of stored norepinephrine. Hence the augmentation by cold of the contractile response to sympathetic nerve stimulation observed in earlier work is not accompanied by an augmentated release of newly synthesized norepinephrine.Acknowledgments. This work was supported by grant HL 05883 from the National Institutes of Health. The authors want to thank F. Jordaens for his valuable technical assistance, J. Beckman for secretarial assistance and H. Hedrickson for preparing the illustrations.Recipient of training grant 80304 from the I.W.O.N.L.     

Depletion of hypothalamic norepinephrine reduces the fever induced by polyriboinosinic acid: polyribocytidylic acid (Poly I:Poly C) in rats

Administration of either Poly I:Poly C (0.05-0.50 micrograms) or norepinephrine (2-8 micrograms) into the anterior hypothalamic area produced a dose-related fever in rats. The fever induced by Poly I:Poly C was attenuated after selective depletion of norepinephrine in the hypothalamus. However, selective depletion of hypothalamic norepinephrine did not affect the fever induced by intrahypothalamic norepinephrine. The data indicate that Poly I:Poly C may act to induce fever through the endogenous release of norepinephrine from the rat's hypothalamus.     

Depletion of hypothalamic norepinephrine reduces the fever induced by polyriboinosinic acid: polyribocytidylic acid (Poly I:Poly C) in rats

Summary Administration of either Poly I:Poly C (0.05–0.50 g) or norepinephrine (2–8 g) into the anterior hypothalamic area produced a dose-related fever in rats. The fever induced by Poly I:Poly C was attenuated after selective depletion of norepinephrine in the hypothalamus. However, selective depletion of hypothalamic norepinephrine did not affect the fever induced by intrahypothalamic norepinephrine. The data indicate that Poly I:Poly C may act to induce fever through the endogenous release of norepinephrine from the rat's hypothalamus.This work was supported by grants from the National Science Council (Taipei, Republic of China).     

Inhibitory action of bradykinin on release of the adrenergic transmitter in the isolated lapine kidney

Summary In the isolated lapine kidney perfused with tyrode solution and prelabeled with [³H] norepinephrine, bradykinin (10 ng/ml) decreased the overflow of tritium elicited by sympathetic nerve stimulation both in the presence and absence of indomethacin. These observations indicate that bradykinin acts at presynaptic sites reducing release of the adrenergic transmitter in the isolated lapine kidney.This study was supported by American Heart Association Grant 77-803, and U.S. Public Health Service Grant HL-16134 from the National Heart and Lung Institute.     

Cholecystokinin-octapeptide-induced hyperthermia in guinea-pigs

Intracerebroventricular administration of cholecystokinin-octapeptide (CCK-8) at room temperature (21 degrees C) induced dose-related hyperthermia in guinea-pigs and also produced hyperthermia at low (10 degrees C) and high (30 degrees C) ambient temperatures. CCK-8-induced hyperthermia was direct and not mediated by prostaglandins, norepinephrine, cyclic AMP or naloxone-sensitive receptors.     

Temperature dependence of neurotransmitter release in the antarctic fish Pagothenia borchgrevinki

The quantal contents of endplate potentials from extraocular muscles of an antarctic fish Pagothenia borchgrevinki were measured over a range of temperatures. Quantal release was maximal at about 5 degrees C but showed little dependence on temperature between -2 degrees C and 10 degrees C. Above 10 degrees C quantal content declined until release ceased about 18 degrees C. In view of the fact that the ambient temperature at which these fish live is constant at -1.9 degrees C, the results suggest that Pagothenia borchgrevinki is only partially adapted to its environment despite 25 million years acclimatization.     

Acute stress reduces the sensitivity of the vasculature to sympathetic control

Summary Vascular smooth muscle from rabbits subjected to acute severe stress exhibits decreased sensitivity to sympathetic regulation. Stimulation of the sympathetic innervation of isolated vascular segments resulted in a similar subsensitivity as did exposure to norepinephrine (NE) but not histamine. Periodic contraction of these segments caused an increase in their maximum ability to contract independent of the constrictor procedure used. These results suggest that the increase in sympathetically mediated NE release that occurs in stress and some other pathological conditions may result in a blunting of neural control and possibly resistance to certain therapeutic agents.Supported by U.S.P.H.S. HL 20581 and GM 7304.     

Hypothermia induced in mice by enzyme-mediated depletion of serotonin

Injection of a purified serotonin (and tryptophan)-degrading enzyme into mice produced a pronounced hypothermia when the mice were maintained at 22 degrees C, but not at 30 degrees C. Brain levels of serotonin and tryptophan were strikingly depleted, but concentrations of norepinephrine and dopamine remained unchanged.     

A rapid electrophoretic method for the separation of hydroxyproline from proline

Summary A rapid, sensitive procedure is described which uses custom made apparatus to separate radioactive imino acids. This technique provides a simple measurement of the distribution of newly synthesized collagen in different fractions.Acknowledgment. This work was supported by grants from the International Wool Secretariat.     

Close relation between hypothalamic and cardiac norepinephrine during stress and its role in acute myocardial infarction disrhythmias

Summary The decrease of the norepinephrine levels in hypothalamus and heart caused by stress is prevented by pargyline and imipramine. Such a decrease in spleen and adrenals is not affected. Chlorpromazine and lithium only prevent the norepinephrine decrease in the spleen. The uptake of H³norepinephrine by isolated atria of guinea-pig increases during anoxia; the change to a normal oxygen situation decreases these norepinephrine levels by more than 50%.     

Dantrolene and the effect of temperature on the spontaneous release of transmitter at the frog neuromuscular junction

The characteristic effect of temperature on m.e.p.p. frequency at the amphibian neuromuscular junction is unaltered by the presence of Dantrolene (an agent that is believed to reduce the efflux of Ca2+ from intracellular stores) or by changes in [Ca2+)o. It is concluded that temperature affects the release system directly, with a transition temperature at about 16 degrees C.     

Existence of different populations of unitary evoked postsynaptic potentials at the frog neuromuscular junction]

The postsynaptic response to monoquantic evoked transmitter release (mean quantal content about 0.3) has been studied at temperatures from 10 to 23 degrees C. The delay between nerve stimulation (1 to 10 Hz) and the unitary postsynaptic potentials fluctuates by steps. The existence of preferential delay sites can always be detected (mean number 13.5 +/- 3.1). Identical delay unitary postsynaptic potentials often shows identical amplitude and identical time to peak. These results suggest that few emitting sites are preferentially activated along the nerve terminal at low level release during long lasting stimulation. The "single process" assumption used in statistical studies of transmitter release is probably oversimplified.     

Newly synthesized elastin is associated with neoplastic epithelial cells in human mammary carcinoma

Summary Indirect immunofluorescence with a purified antiserum to human foetal elastin has identified newly synthesized elastin on the membranes of neoplastic epithelial cells in human mammary carcinoma.This research was supported by a project grant from the Medical Research Council, London.     

Activation by S-adenosylhomocysteine of norepinephrine and serotonin in vitro uptake in synaptosomal preparations from rat brain.

S-Adenosylhomocysteine (10(-7)-10(-5) M) activated norepinephrine (NE) and serotonin (5HT) in vitro uptake in synaptosomal preparations from rat brain, but did not affect dopamine (DA) uptake. When administered to rats (7 mg/kg i.p.), it has the same effect on in vitro NE and 5HT uptake. It did not affect NE and 5HT release.     

Role of calcium in the histamine release induced by D-galactosamine from rat mast cells

Rat peritoneal mast cells were isolated and purified by differential centrifugation in Ficoll. Cells pooled from three to four rats were suspended at approximately 10(6) cells/ml in a buffered salt solution and incubated for 1 h at 37 degrees C in 300 microliter volumes in the absence or presence (9 X 10(-4) M) of calcium chloride. Addition of D-galactosamine hydrochloride (DGM; 2.8 X 10(-4)M) caused (in addition to basal release) a mean +/- SEM percent histamine release of 15.7 +/- 5.2 in the presence of Ca++ and 19 +/- 4.9 in the absence of Ca++ (p greater than 0.05). It is suggested that D-galactosamine does not require extracellular Ca++ for the release of histamine from the rat mast cell.     

Studies on substrate specificity of X-prolyl dipeptidyl-aminopeptidase during new chromogenic substrates, X-Y-p-nitroanilides

Substrate specificity of X-prolyl dipeptidyl-aminopeptidase (dipeptidyl aminopeptidase IV) was examined by using newly synthesized 8 chromogenic substrates, X-Y-p-nitroanilides. Homogeneous enzyme from human submaxillary gland hydrolyzed glycylproline p-nitroanilide almost specifically, except alanylalanine p-nitroanilide which had 11% activity.     

Alpha 1-adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

The effect of norepinephrine on fatty acid synthesis (3H2O incorporation into fatty acids), on fatty acid oxidation to CO2 and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 microM), lipogenesis was lower (5.7 +/- 1.1 nmoles 3H2O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5 +/- 1.7; n = 6, p less than 0.02). In contrast, (1-14C) palmitate conversion into total ketone bodies was increased to 10.9 +/- 1.8 nmoles/mg/30 min with norepinephrine, vs 8.5 +/- 1.6 in controls (p less than 0.05), and more (1-14C) palmitate was converted to 14CO2 with norepinephrine than in controls (1.48 +/- 0.10 nmoles/mg/30 min vs 1.06 +/- 0.11, p less than 0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the alpha 1-receptor blocker prazosin, but not by alpha 2 or beta-blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

Control of pituitary secretion of melanotropin in an anuran amphibian by thyrotropin releasing factor (TRH). Study in vitro]

Intermediate lobes from Rana esculenta pituitary glands were continuously superfused for 7 hrs at 28 degrees C with amphibian culture medium. alpha-MSH release was measured by use of a sensitive double antibody radio-immunoassay system. alpha-MSH secretion was inhibited by low temperatures. A large increase in alpha-MSH release was observed when Thyrotropin Releasing Hormone (TRH) at doses ranging from 10(-9) to 10(-7) molar was added to the superfusion medium. Since large amounts of TRH are to be found in the hypothalamus of amphibians but have no effect over pituitary TSH secretion, the action of TRH over alpha-MSH release may have a physiological significance.     

Studies on substrate specificity of X-prolyl dipeptidyl-aminopeptidase using new chromogenic substrates,X-Y-p-nitroanilides

Summary Substrate specificity of X-prolyl dipeptidyl-aminopeptidase (dipeptidyl aminopeptidase IV) was examined by using newly synthesized 8 chromogenic substrates, X-Y-p-nitroanilides. Homogeneous enzyme from human submaxillary gland hydrolyzed glycylproline p-nitroanilide almost specifically, except alanylalanine p-nitroanilide which had 11% activity.     

Cathepsin D and the catabolic degradation of proteoglycans in granulomatous tissue]

Incubated in vitro at 37 degrees C, granulation tissues release glycosaminoglycans into the incubation medium. Such release is inhibited if pepstatine is present in the medium. From this result, it can be inferred that the protien moiety of the proteioglycans is degraded by cathepsin D. Therefore a role of this enzyme in granulation tissues appears, especially in the late reparative phase.