The effect of growth hormone on biogenic amines in the hepatic portal circulation of the dog

The effects of a spike concentration of growth hormone (GH) on hepatic portal and peripheral levels of free serotonin and catecholamines were studied by improved radioenzymatic methods in trained, conscious, normal, adult dogs fitted with an indwelling portal catheter. An injection of ovine GH (6 or 100 micrograms/kg) into a cephalic vein produced in the hepatic portal circulation a transient, statistically significant rise of serotonin and a concomitant significant reduction in the concentration of dopamine, norepinephrine, and epinephrine. No change was found in the peripheral circulation, partly because the amines were conjugated to sulfates and glucuronides and these derivatives are not detectable by our assays. Thus, a pulse of GH not only stimulates the release of pancreatic hormones and glucose turnover, but also affects the portal profile of glucoregulatory bioamines. The present investigation lends further support to our view that the splanchnic area represents an endocrine system whose preferential target is the liver.     

The effect ofl-deprenyl on behavior,cognitive function,and biogenic amines in the dog

Behavioral and pharmacological effects of oral administration ofl-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected byl-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested thatl-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects ofl-deprenyl on behavior and cognitive function.     

Effects induced hypothermia on hepatic portal circulation

Studies of the liver circulation in dogs during hypothermia, showed that portal blood flow is reduced with no significant changes of blood pressure and with important vascular resistance. These effects are probably due to the contraction of pre-capillaries sphincters.     

Selective effect of microembolization on pulmonary removal of biogenic amines

Pulmonary amine extraction (E) was measured by triple-indicator dilution techniques from bolus injections of trace amounts of 5-hydroxy[14C]tryptamine ([14C]HT)m [3H]norepinephrine ([3H]NE), indocyanine green dye before and after glass-bead embolization in 23 anesthetized dogs. Control E(5-[14C]-HT) was 89.7 +/- 1.7%; 10 min after embolization (which approximately doubled pulmonary artery pressure and pulmonary vascular resistance), E(5-[14C]HT) was significantly reduced to 65.9 +/- 3.0% (kappa +/- SE; n = 10) (P less than 0.01). Control E([3H]NE) (40.1 +/- 4.5%) was unaffected by embolization. Imipramine (8 mg/kg) depressed control E(5-[14C]HT) to 38.7 +/- 1.5% and control E([3H]NE)d to 35.0 +/- 3.9% (P less than 0.05; n = 4). In these animals, pulmonary hemodynamic changes secondary to embolization were comparable to those in non-drug-treated dogs, but E(5-[14C]HT) and E([3H]NE) were not further depressed. Progressive pulmonary lobar artery ligation (n = 5) did not affect amine extraction until perfusion was limited to one lobe. The selectivity of the effect of embolization on E(5-[14C]HT), the lack of an effect on imipramine-insensitive E(5-[14C]HT) extraction, and the much smaller changes after progressive lobar ligation indicate that, although derecruitment of vascular surface area secondary to mechanical obstruction may contribute to postembolization depression of E(5-[14C]HT), additional mechanisms such as local saturation of 5-HT uptake or selective damage to endothelial cell transport of 5-HT may underlie these observations.     

Somatostatin mediates the effect of growth hormone surges on splanchnic biogenic amines

Experiments were conducted in trained, conscious dogs fitted with an indwelling portal catheter. Radioenzymatic methods were employed for the quantitative measurement of plasma-free serotonin and catecholamines. An injection of ovine growth hormone (GH, 100 micrograms/kg) or an equimolar amount of somatostatin (somatotropin release inhibitory factor, SRIF, 7.5 micrograms/kg) into a saphenous vein led, within the first 15 min, to a transient but significant increase in plasma serotonin and a decrease in the concentrations of dopamine, norepinephrine, and epinephrine. The changes were frequently in excess of 40% of baseline values, and were found only in the portal and not in the peripheral circulation. When the animals were pretreated with an antiserum specifically directed against SRIF, GH surges no longer caused alterations in the portal levels of biogenic amines. Thus, the effects of spike concentrations of GH on plasma serotonin and catecholamines are apparently mediated by SRIF, a novel and unexpected function for a hormone that is known as an inhibitor of GH secretion.     

The effect of colchicine, cyclic nucleotides and biogenic amines on the taste receptor apparatus

Frog tongue chemoreceptors, under the influence of colchicine,show a decrease in reaction to adequate stimuli. This effectis reversible and eliminated by injection of 3',5'-cAMP, GTP,theophilline and adrenaline. Other nucleotides appear to beineffective in reversing this effect. 5'-Hydroxytryptamine,inosine, acetyl-choline and 3',5'-GTP alter receptor responsesbut do not restore colchicine-blocked reactions. It is suggestedthat the colchicine-sensitive, 3' ,5'-cAMP-dependent processplays an important part in the maintenance of normal chemoreceptorreactivity to adequate stimuli.     

Insulin dependence of the actions of growth hormone and somatostatin on splanchnic biogenic amines of the dog

It is known from studies previously conducted in this laboratory that an iv injection of ovine growth hormone (GH, 100 micrograms/kg BW) or an equimolar amount of somatostatin (SRIF, 7.5 micrograms/kg BW), given to normal conscious dogs into a saphenous vein, leads to a significant increase in hepatic portal plasma serotonin and a simultaneous decrease in the concentrations of dopamine, norepinephrine and epinephrine. The changes take place within 12 minutes after the injection and are observed only in the portal circulation. The purpose of the present experiment was to investigate whether or not similar results could be obtained in diabetic animals. Mongrel dogs were rendered diabetic by surgical pancreatectomy and fitted with an indwelling hepatic portal catheter. Radioenzymatic methods were employed for quantitative measurements of plasma free serotonin and catecholamines. No response was noted when the same type of experiments as those conducted in normal dogs were now carried out in trained, fully conscious totally pancreatectomized dogs deprived of exogenous insulin supply. When the same animals were given an injection into a peripheral vein of 50 mU/kg BW regular crystalline insulin (a small dose that affected neither plasma glucose nor biogenic amine levels) 10 minutes prior to the administration of the other hormones, the usual response to both GH and SRIF was restored, i.e. the data were comparable to those of normal dogs. It is concluded that the GH/SRIF effect on gut biogenic amines is insulin dependent.     

Microiontophoretic study of the effect of biogenic amines on unit activity in the rabbit visual cortex

The effect of acetylcholine, noradrenalin, and serotonin on spontaneous activity of visual cortical neurons and on their activity evoked by flashes, recorded extracellularly, was studied by microiontophoresis in unanesthetized rabbits. The ability of visual cortical neurons to respond to light does not correlate with their sensitivity to acetylcholine. This substance, which changes the spontaneous firing rate of many of the neurons tested, was less effective against their evoked activity. Noradrenalin had a powerful depressant action on both spontaneous and evoked activity of most neurons studied. Serotonin acted in different ways on the spontaneous and evoked activity of some neurons tested. It is postulated that acetylcholine mediates reticulo-cortical inputs, noradrenalin is a true inhibitory mediator in the cerebral cortex, and serotonin has a presynaptic action by preventing the liberation of natural mediators.     

The value of the fluorescence histochemistry of biogenic amines in neurotoxicology

Conclusions Acid- and aldehyde-induced fluorescence offers a highly sensitive and specific instrument for the histochemical demonstration of biogenic amines. This technique can be used to advantage for the selective identification of those neuronal structures that contain biogenic amines, namely the peripheral postganglionic sympathetic neurones and the central aminergic neuronal systems.Structural changes of impaired aminergic neurones can be ascertained from their fluorescence microscope image and correlated with light and electron microscopical observations, so that selective neurotoxic changes, such as sympathetic denervation of organs, can be detected and the reversibility of these changes tested.The degree of functional and structural changes occurring in the above neuronal systems can be easily quantified by means of microfluorimetry.The histochemical approach is restricted by the necessity of using fresh and specially fixed tissues. The possibility of numerous pitfalls in the interpretation of histochemical reactions requires the simultaneous use of other optical methods, such as light and electron microscopy, or the testing of the uptake of exogeneous amines or their precursors, whenever the occurrence of neurotoxic effects is to be assessed.     

Polymers of biogenic amines.

Biogenic amines, with a primary amino group, were reacted with glutaraldehyde to form insoluble precipitates. These precipitates had distinctive ultrastructural features upon further reaction with osmic acid. When tested in vitro, they had biological activity and showed evidence that part of this biological activity was due to the large polymer of glutaraldehyde and amine. Experiments with isotope-labelled amines in the production of these precipitates showed that the precipitated polymers were not completely stable and that free amine was liberated from them. Since they were not stable, , they could not be used for the morphological localization of the amines as had been intended, but they may have some use as depot drugs or in the immunization of animals against these amines.