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O Isaksson

Publications and source records attributed to O Isaksson.

At least 73 records · Page 4Linked to original sources

Plasma levels of growth hormone in female rats of different ages.

Radioimmunoassayable growth hormone (GH) was determined in fed and fasted female rats of different ages. In 6-40 day-old rats blood was collected at hourly intervals in groups of rats at different time intervals during the day. Within each age group the variation in plasma GH was considerable. In 6-14 day-old rats plasma GH was generally elevated. By day 18 levels declined, lowest on day 22 and by day 26 again increasing. In 14 day-old rats the median plasma level of GH was 22 ng/ml, in 22 day-old rats less than 5 ng/ml and in 40 day-old rats 43 ng/ml. In 14 day-old rats levels ranged from less than 5 ng/ml--148 ng/ml, in 22 day-old rats from less than 5 ng/ml--34 ng/ml and in 40 day-old rats from less than 5 ng/ml--greater than 200 ng/ml. A 20 h fasting period was associated with a significant decrease in plasma GH. In 45 day-old rats, the variations in plasma GH of individual animals were studied by obtaining sequential blood samples from unrestrained, undisturbed animals with implanted intra-aortic cannulae. In these rats GH secretion was characterized by an episodic release, occurring every 2--4 h. After a 20 h fasting period major peaks were depressed and occurred less frequently. It is concluded that there is an age-related as well as a circadian rhythm in growth hormone secretion in the rat and that sequential sampling of blood is essential for the evaluation of the secretory pattern.

Aging↗

Effect of insulin and adrenaline on cyclic AMP in the diaphragm of normal and diabetic rats.

The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline. The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin.

Animals↗

Human adipose tissue in culture. IV. Evidence for the formation of a hormone antagonist by catecholamines.

Explants of human adipose tissue were cultured for several days with noradrenaline (NA). After the culture period the explants were carefully washed, preincubated and then incubated for 2 h by a technique analogous to those generally used to study adipose tissue metabolism. The results show that explants cultured with NA were considerably less responsive to the acute lipolytic effect of catecholamines than explants not previously exposed to NA. The diminished responsiveness could not be reversed by the addition of phentolamine or by preincubating the explants with a prostaglandin antagonist and it was dependent upon the concentration of noradrenaline used in the culture medium as well as upon the period of time that the explants were exposed to the hormone. The cyclic AMP (cAMP) levels did not increase in response to NA in these explants. Addition of theophylline or dibutyryl cAMP elicited a lipolytic response. However, the phosphodiesterase levels were not increased in the explants cultured with noradrenaline. When freshly excised tissue specimens were incubated in the culture medium which had previously contained NA the acute lipolytic effect of catecholamines was blunted. The results indicate that an antagonist is formed during the incubation with NA which inhibits the responsiveness to catecholamines. The effect of the antagonist seems to be exerted at a step prior to the formation of cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗

Development of responsiveness of young normal rats to growth hormone.

Growth hormone (GH) exerts a biphasic effect on the membrane transport of amino acids and sugars in diaphragms from hypophysectomized rats. A stimulatory (insulin-like) effect of GH is observed for approximately 3 hr after the administration of the hormone, and then the diaphragm becomes "refractory" to further administration of the hormone for 24-48 hr. In the present study the in vitro responsiveness of diaphragms from young normal rats of different ages to bovine growth hormone (bGH) was studied by measuring the accumulation of alpha-aminoisobutyric acid (AIB), cycloleucine, and 3-0-methyl-glucose (3-OMG) and by determining the incorporation of phenylalanine into diaphragm proteins. bGH increased the uptake of AIB in 6, 10, 14, 18, and 22-day old and of cycloleucine in 10, 14, and 18-day old rats, respectively. The maximal stimulatory effect was seen in 18-day old rats and no effects were seen in 26 and 30-day old animals. A similar pattern of age-related responsiveness was also seen when the uptake of 3-OMG and the incorporation of phenylalanine were studied. The rate of accumulation of the nonutilizable amino acids, as well as the rate of incorporation of phenylalanine, decreased markedly with age. Fasting the rats for 20 hr did not change the principal age-related responsiveness of AIB transport to GH, but the magnitude of the hormone effect increased due to a lower uptake of AIB in control diaphragms. bGH had a dose-dependent effect on the accumulation of AIB in fasted 18-day old rats, the threshold concentration of bGH being 0.1 mug/ml. When diaphragms from 18-day old rats were incubated with bGH for various periods, the uptake of AIB was stimulated between 0 and 60 and 120 and 180 min, but not between 60 and 120 min after the start of the incubation. This observation indicated that the muscles were "refractory" to GH between 60 and 120 min. Preincubation of diaphragms from 21-day old rats with bGH for 3 hr did not inhibit the stimulatory effect of bGH added subsequently indicating that the duration of the "refractory phase" did not exceed 270 min in this group of rats. When diaphragms from fasted rats of different ages were preincubated in Krebs bicarbonate buffer for 3 hr, a stimulatory effect of bGH on AIB uptake was also observed in 26 and 30-day old rats, possibly because the influence of endogenous GH subsided during the preincubation period. These results suggest that diaphragms from "old" normal rats are insensitive to exogenous GH because the "refractory phases" become considerably prolonged with age.

Age Factors↗

Effect of adrenaline on the release of cyclic AMP by the rat diaphragm.

An investigation was made of the effect of adrenaline on the tissue level and release of cyclic AMP (cAMP) into the incubation medium by the isolated rat diaphragm preparation. Adrenaline, added in vitro, caused a dose-dependent biphasic increase in the tissue level of the nucleotide. A significant elevation of the level of cAMP in the tissue was observed throughout a 60 min incubation period in the presence of 0.01, 0.1 and 10 mug/ml of adrenaline. The hormone also produced a small but significant increase in the release of cAMP into the incubation medium. The accumulation of cAMP in the incubation medium ceased after 10 min of incubation in the presence of adrenaline, although the tissu e level of the nucleotide remained considerably elevated throughout the entire incubation period. Theophylline potentiated the effect of adrenaline on both the accumulation of cAMP in the tissue and in the incubation medium. Theophylline by itself also increased the tissue level of cAMP slightly. It is concluded from the present study that the elimination of cAMP from the rat diaphragm muscle by release of the nucleotide from the cells is small.

Animals↗

Effects on myocardial contractility of blood-borne material released from the feline small intestine in simulated shock.

There is a pronounced derangement in cardiovascular function in the cat after a 2- or 3-hour period during which shock is simulated in the small intestine by regional hypotension (BP = 30-35 mm Hg) during activation of vasoconstrictor nerve fibers. It has been proposed that these effects are caused by blood-borne cardiode-pressant substance(s) released from the "shocked" small intestine. To obtain further evidence for this hypothesis we performed a study on two heart preparations in vitro. Rabbit papillary muscles or isolated beating rat hearts were exposed to intestinal venous plasma obtained from control cats and from cats subjected to simulated intestinal shock for 2 or 3 hours. while control plasma induced only a slight depression of myocardial contractility, plasma from "shocked" intestine caused a significant decrease in peak isometric tension of the papillary muscles or a fall in systolic pressure of the rat hearts. Since the experiments on papillary muscle indicated that time to peak tension was largely unaffected by the plasma samples, we conclude that the feline intestine in shock releases material into blood that exerts a negative inotropic effect on the myocardium.

Animals↗

Levels of cyclic AMP and electrical events during inhibition of contractile activity in vascular smooth muscle.

The possible relationship between changes in electrical and mechanical activity and in tissue levels of cyclic AMP (cAMP) during relaxation of the myogenical active rat portal vein has been elucidated in response to different inhibitory stimuli. Isoproterenol, 10(-5) M, caused an initial pronounced inhibition of spike discharge and contractions followed by a partial recover over the 15 min exposure period. This inhibitory response was associated with doubling of tissue cAMP after 1 min and a less pronounced increase in later measurements (5 and 15 min). Papaverine, 10(-4)M, caused, in contrast, an inhibition of electrical and mechanical activity which developed gradually over the entire 15 min exposure period. The levels of cAMP at 1,5 and 15 min all exceeded the corresponding values obtained with isoproterenol. The two drugs in combination gave a biphasic inhibitory response associated with a sustained large increase in the level of cAMP. These drug induced inhibitions were thus accompanied by increased levels of cAMP, but the different time courses of the electromechanical responses could not be rlated to corresponding variations in the content of cAMP. Hyperosmolality (+150 mM sucrose) and mechanical vibration (100 Hz) elicited differentiated inhibitions of smooth muscle activity without changes in tissue cAMP. The mechanical effects elicited by isoproterenol, papaverine and hyperosmolality were accompanied by approximately parallel changes in electrical spike discharge. It is concluded that increased levels of cAMP are not indispensible for vascular smooth muscle relaxation, and that the magnitude of pharmacologically induced inhibitions are not always closely related to the total tissue content of the nucleotide.

Animals↗

Consequences of myocardial structural adaptation on left ventricular compliance and the Frank-Starling relationship in spontaneously hypertensive rats.

The Frank-Starling relationship of hearts from adult spontaneously hypertensive rats (SHR, Okamoto 1969), representing the established phase of hypertension, and of young SHR, representing the initial phase of hypertension, was investigated by using the isolated working heart preparation. In the "normal" diastolic pressure range (5 to 10 cm H2O), the left ventricle of both SHR groups displayed significantly reduced stroke volumes compared with hearts of normotensive controls (NCR); the degree of reduction being proportional to the left ventricular hypertrophy. This is suggested to be due to a reduced left ventricular diastolic compliance in SHR, as indicated by direct measurements of ventricular wall thickness and end-diastolic volumes in arrested hearts exposed to different end-diastolic filling pressures. Such a progressive shift of the Frank-Starling relationship to the right with duration of hypertension could, in combination with the gradual development of "structural autoregulation" of the precapillary resistance vessels, constitute dominating factors in shifting the hemodynamic situation in labile hypertension into that characterizing the established, or "fixed", state of hypertension.

Adaptation, Physiological↗

Characterization of the metabolism of exogenous cyclic AMP by perfused rat heart and incubated prepubertal rat ovary.

In order to study the metabolism of extracellular 3',5'-adenosine monophosphate (cAMP), rat hearts were perfused and prepubertal rat ovaries incubated with 3H- and 32P-labelled cAMP (0.025-1 muM). The rate of disappearance of cAMP from the medium was determined by "Ba-Zn-precipitation" and degradation products of 3H- and 32P-CAMP by paper chromatography. Both tissues degraded cAMP to 5'-adenosine monophosphate (AMP), but the enzyme kinetic for this phosphodiesterase activity was different (apparent Km value for the heart 3.95 muM and for the ovary 0.2 muM). AMP was further degraded, since also other labelled substances were found in the medium. An uptake of both 3H- and 32P-labelled substance(s) into the heart and the ovary was noticed. Tissue extracts contained several labelled purines, but the amounts of labelled cAMP did not exceed expected amounts in the extracellular space. In the ovary the uptake of cAMP and AMP seemed to be low, since the uptake of labelled substances was inhibited by high concentrations of unlabelled AMP or adenosine. The degradation of 32P-cAMP was unchanged when AMP was present, strongly suggesting that the phosphodiesterase enzyme was acting extracellularly. In the heart added AMP was very rapidly degraded making it impossible to elucidate whether cAMP was degraded extracellularly or not. It is concluded that elimination of extracellular cAMP under physiological conditions can be due to degradation of cAMP by various tissues. At least for the ovary this phosphodiesterase enzyme is extracellularly active.

Adenine↗