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A Sirek

Publications and source records attributed to A Sirek.

At least 19 recordsLinked to original sources

Hypophysectomy does not alter the effects of somatostatin or growth hormone on canine splanchnic biogenic amine release.

We have demonstrated previously that growth hormone (GH) and somatostatin (somatotropin release inhibitory factor, SRIF) exert comparable effects on the release of splanchnic biogenic amines. The purpose of the present investigation was to study further the response of the two hormones and see whether the similarity persists in dogs completely deprived of endogenous GH. Experiments were conducted in seven hypophysectomized dogs fitted with an indwelling portal catheter. Two to 4 weeks after surgery the responsiveness of their catecholaminergic neurons was tested by an injection of human beta-endorphin (20 micrograms/kg); it caused a rise in portal catecholamine levels equivalent to that seen in intact dogs. Then the effect of a spike concentration of SRIF or GH on hepatic portal and peripheral levels of free serotonin and catecholamines was studied, all by radioenzymatic methods. The intravenous injection of ovine GH (100 micrograms/kg) or equimolar amounts of SRIF (7.5 micrograms/kg) produced in the hepatic portal circulation a transient but statistically significant rise of serotonin and a concomitant reduction in the concentration of dopamine, norepinephrine, and epinephrine. No changes were found in the peripheral circulation. The response patterns to SRIF or GH were virtually identical, which is in keeping with our other data, suggesting that the effect of GH on splanchnic biogenic amine secretion is SRIF-dependent and mediated by SRIF-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Secretory pattern of canine growth hormone.

Our aim was to define the secretory pattern of growth hormone (GH) under basal conditions in fasted, conscious, male dogs accustomed to handling. Blood samples were withdrawn from a cephalic vein at 15-min intervals. In this way, any ultradian rhythms, if present, could be detected within the frequency range of 0.042-2 cycles/h. In addition, samples were drawn at either 1- or 2.5-min intervals for 2.5 or 5 h to determine whether frequency components greater than 2 cycles/h were present. GH was measured by radioimmunoassay and the raw data were submitted to time series analysis employing power spectral estimation by means of fast Fourier transformation techniques. Peak plasma levels were up to 12 times higher than the baseline concentration of approximately 1 ng/ml. Spectral analysis revealed an endogenous frequency of 0.22 cycles/h, i.e., a periodicity of 4.5 h/cycle. The results indicate that under basal conditions the secretory bursts of canine GH are limited to one peak every 4.5 h.

Animals↗

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.

Animals↗

The effect of beta-endorphin on biogenic amines, insulin, and glucagon levels in the hepatic portal circulation of normal and pancreatectomized dogs.

The effect of peak concentrations of beta-endorphin on hepatic portal and peripheral levels of plasma catecholamines, free serotonin, glucose, insulin, and glucagon was studied in trained, conscious, normal adult dogs fitted with an indwelling portal catheter. An injection of synthetic human beta-endorphin (20 micrograms/kg BW) into a cephalic vein produced a significant rise in the portal concentration of dopamine, norepinephrine, and epinephrine. The rise was accompanied by a reduction of portal free serotonin levels. The changes were not seen in the peripheral circulation. No appreciable changes in plasma insulin, glucagon, and glucose concentrations were noticed either in the hepatic portal or in the peripheral circulation. The response of the biogenic amines to beta-endorphin was abolished by pretreatment with Naltrexone (1 mg/kg BW). A dose of somatostatin antiserum given before beta-endorphin did not alter the biogenic amine response to the opioid peptide. When beta-endorphin was administered to pancreatectomized dogs devoid of exogenous and endogenous insulin supply, the biogenic amine response remained virtually the same as in normal intact dogs. It is concluded that in the dog a pulse of beta-endorphin causes profound alterations of splanchnic biogenic amine concentrations that are independent of the ambient levels of insulin, somatostatin, and pancreatic glucagon.

Amines↗

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.

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The effect of tryptophan on biogenic amines in the hepatic portal circulation of the dog.

Mongrel dogs were fitted with indwelling hepatic portal catheters. After recovery from surgery, experiments were conducted in fasting, unrestrained, fully conscious, normal dogs which were accustomed to handling and withdrawal of blood samples. L-Tryptophan, a specific serotonin precursor, was injected into a saphenous vein, 10 microM/kg body weight, dissolved in saline. Plasma serotonin, dopamine, norepinephrine, and epinephrine were determined by radioenzymatic assays in blood samples withdrawn at frequent intervals for 2 h, simultaneously from the indwelling catheter and from a catheter temporarily inserted into a saphenous vein other than the one used for the injection of tryptophan. The injection of the amino acid caused a significant elevation of the concentration of platelet-free serotonin within 60 min and this was accompanied by a reduction in the concentration of the catecholamines, dopamine, norepinephrine, and epinephrine. The changes occurred only in the portal circulation and were not detected in peripheral blood samples. The results of these experiments indicate the existence of a cause and effect related interdependence between the splanchnic serotonergic and adrenergic systems in that the tryptophan-stimulated increase in serotonergic activity resulted in a concomitant reduction in gut adrenergic activity.

Animals↗

Secretory patterns of glucoregulatory hormones in prehepatic circulation of dogs.

The temporal organization of patterns of secretion of insulin, glucagon, and somatostatin was studied in basal conditions in normal or pancreatectomized dogs fitted with an indwelling hepatic portal catheter. Portal and peripheral blood samples were collected at a 7.5- or 15-min frequency, which covered the medium range of the ultradian period. The raw data were studied using spectral analyses employing fast Fourier transformation (FFT) techniques. The results indicate that in normal dogs: 1) endogenous physiological periodicities, statistically significant at a level of alpha = 0.05 (i.e., 95% confidence interval), were found to exist for the three pancreatic hormones in portal blood between 0.54 and 1.78 h/cycle and in peripheral blood between 0.59 and 1.84 h/cycle; 2) the portal levels of the hormones are significantly higher than peripheral ones; and, 3) whereas pancreatic hormones oscillated, glucose was found to maintain a steady level. In pancreatectomized dogs, no regular rhythm was detected. Thus, whereas endogenous periodicities exist for the secretion of pancreatic hormones in the normal dog, in the pancreatectomized dog the extrapancreatic glucagon and somatostatin are secreted in nonperiodic, randomly occurring pulses.

Animals↗

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.

Animals↗

Rapid changes in hepatic glucose output after a pulse of growth hormone in dogs.

In response to a single intravenous injection of bovine growth hormone (GH, 100 micrograms/kg) the non-steady-state turnover of glucose, as well as portal levels of insulin (IRI), glucagon (IRG), somatostatin (SRIF), and glucose were determined in normal conscious dogs. Using the two-compartment model validated to calculate rapid turnover changes and tracer infusion methods, the rate of hepatic output of glucose [Ra(t)] was found to be increased, reaching a maximum of 224 mg/min, 7.4 times the basal rate, 4 min after injection of GH. Ra(t) returned to its basal level 35 min later in a damped oscillatory manner. Hormone determinations were carried out in portal venous blood drawn every 2 min for 2 h from an indwelling catheter. IRG peaked 2 min after GH injection and levels of IRI, SRIF, and glucose peaked between 4 and 8 min. Hormone concentrations returned to normal, i.e., were oscillating around base-line levels, about 30 min after GH. These experiments demonstrate for the first time in vivo that a pulse of GH causes transient changes of glucose turnover and measurable alterations of the hormonal homeostasis in the splanchnic area.

Animals↗

Growth hormone stimulates serotonin secretion into the hepatic portal circulation.

Hepatic portal plasma concentrations of free serotonin were found to be transiently but significantly elevated in normal dogs following a single injection of ovine growth hormone into a peripheral vein. The data are consistent with the concept that spike concentrations of growth hormone are capable of altering the splanchnic concentration of agents that are concerned with glucose homeostasis.

Animals↗

A new technique for hepatic portal sampling in the conscious dog.

A technique for implantation of a silastic catheter into the portal vein is described. The central end of the catheter is passed through a puncture hole into a tributary of the portal vein. The peripheral free end, occluded by a rubber membrane, is passed through the abdominal wall and buried under the skin. Once the catheter is in place it can be kept patent for several weeks. Injection of a substance and withdrawal of blood from the portal vein are carried out by percutaneous puncture of the rubber membrane, a virtually painless procedure that can be carried out in fully conscious nonrestrained dogs.

Animals↗

Arterial glycosaminoglycans in diabetic dogs.

The glycosaminoglycan (GAG) composition of a number of large and medium-sized arteries was studied in 6 alloxan-diabetic beagles and was compared with 6 normal, age-matched controls. Diabetic animals were maintained on diet and insulin for 100 days. The aortic arch, thoracic and abdominal segments, external iliac, superior mesenteric, renal, common carotid and coronary arteries were analyzed for hyaluronic acid (HA) and for heparan (HS), dermatan (DS), and chondroitin (CS) sulphates. All diabetic dogs displayed significant alterations. The HA content was reduced in iliac arteries, and together with HS, also in the thoracic aorta. HS or CS were increased in carotid, iliac and renal arteries, DS, a GAG constitutent with very high affinity for low density lipoproteins, was significantly increased in coronary arteries alone. 2 additional animals which are excluded from this series did not become diabetic after alloxanization and showed no change in arterial GAG content. Early changes in the chemistry of the arterial ground substance seem to provide a clue to the precocious development of atherosclerotic disease in diabetes.

Animals↗

Diurnal episodic pattern of insulin secretion in the dog.

Sampling portal blood every 15 min by means of indwelling cannulae, we have found evidence that basal insulin secretion in nonanesthetized dogs takes place in six or seven major secretory episodes over a 24-h period. Reproducible patterns were obtained in four experiments conducted on three normal animals. When frequency of peaks was plotted against the log of insulin concentration, a normal distribution was obtained (lognormal distribution). The means and variances were nearly the same in the three animals. Low levels of insulin (10--25 microU/ml) alternated with peaks which were occasionally higher than 200 microU/ml. The average duration of a peak was 30 min and seemed to be independent of ambient glucose levels. It is suggested that these peaks are the result of surges in plasma growth hormone concentrations and/or spontaneous repetitive discharges along neuronal pathways functionally related to insulin secretion.

Animals↗

Effect of growth hormone on acute glucagon and insulin release.

The aim was to clarify whether or not sudden spike concentrations of plasma growth hormone (GH) can affect the endocrine pancreas in vivo. The peaking of GH was reproduced by an injection (10 mg/kg iv) of bovine GH to anesthetized normal, pancreatectomized, and alloxan-diabetic dogs. In portal but not in peripheral blood, immunoreactive plasma glucagon (IRG), glucagon-like activity (GLI), and immunoreactive insulin (IRI), were significantly elevated within 10 min in normal and alloxan-diabetic dogs. In pancreatectomized dogs, GH did not affect either IRG or GLI. When a physiological dose of GH (6 microgram/kg) calculated to produce ambient peak plasma concentrations of 40 ng/ml was given to four conscious, normal dogs with indwelling portal catheters, a rise of IRG from 108 +/- 19 to 170 +/- 17 pg/ml and of IRI from 20 +/- 12 to 67 +/- 19 muU/ml (mean +/- SE) occurred within 2 min. GLI was not affected. Thus a sudden rise in GH concentration can stimulate the release of a) GLI in the presence but not in the absence of the pancreas, and b) pancreatic IRG and IRI but not extrapancreatic IRG.

Animals↗

Diabetes, dietary tryptophan, and protein intake regulation in weanling rats.

The effects of streptozotocin-induced diabetes and tryptophan content of the protein fed on protein intake regulation by weanling rats selecting from 10 and 60% casein diets were evaluated. In uncompensated diabetes the ratio of tryptophan to other selected neutral amino acids in plasma and brain tryptophan were reduced, protein intake per unit of body weight was increased, and serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were unaffected. Enrichment of the tryptophan content of the ingested protein caused a decrease in protein, but not energy consumption of both diabetic and nondiabetic rats. The reduction in protein intake correlated inversely with increases in the tryptophan content relative to the neutral amino acids in plasma and with increases in brain tryptophan and serotonin levels in both diabetic and nondiabetic rats. The data suggest that protein-feeding behavior is regulated by a mechanism that includes brain serotonergic activity with insulin, through its influence on circulating amino acids, determining the quantity of protein consumed in relation to body weight.

Animal Population Groups↗

Effect of hormones on the glycosaminoglycan content of canine renal arteries.

The effect of hypophysectomy and replacement therapy with individual hormones such as somatotropin, cortisone, estradiol, progesterone and testosterone on the glycosaminoglycan (GAG) composition of renal arteries was studied in young beagles. The renals from normal animals showed a uniformly low total GAG content of about two thirds of the value found for aorta and coronary arteries. Neither hypophysectomy nor hormone replacement altered the GAG content, with the exception of estradiol which showed a marked effect by raising the hyaluronic acid content to nearly double the normal value. These results by being at variance with those obtained for aorta and coronary arteries provide further evidence of the differential hormone sensitivity that exists in the various segments of the canine arterial tree with respect to GAG metabolism.

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