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Biomedical subjects

D O Allen

Publications and source records attributed to D O Allen.

At least 37 records · Page 2Linked to original sources
PubMed1977

Perifused adipose cells, quantitation and kinetics of lipolysis.

The perifused fat cell system is a system with which lipolytic activity can be monitored on a minute-to-minute basis. Thus, the rate at which lipolysis changes following the addition and removal of hormones can be followed. Catecholamines and other lipolytic agents produced a time-dependent increase in lipolysis following addition of agents, and a time-dependent decrease in lipolysis occurred following removal of the agent. ACTH also produced an increase in lipolysis. However, on termination of ACTH infusion, the lipolytic rate did not return to basal level but remained elevated for at least an additional 30 min (persistent phase). The persistent phase could be terminated by removal of Ca2+. Readdition of Ca2+ in the absence of additional ACTH resulted in a rapid increase in glycerol release. No persistant phase occurred following ACTH if the adipocytes were perifused in a Ca2+-free buffer. However, if Ca2+ was added to the system 20 min after termination of ACTH infusion, lipolysis increased to a rate greater than that obtained initially by infusing ACTH in a Ca2+-free buffer. It is concluded that ACTH is bound to some component of the fat cell in a Ca2+ independent, tenacious manner, and the full manifestation of that binding is dependent on the presence of Ca2+.

Adipose Tissue↗
PubMed1976

On the lipolytic action of parathyroid hormone in man.

An investigation was carried out to determine whether bovine PTH stimulates lipolysis in human fat tissue, whether this action is mediated by cyclic adenosine 3', 5'-monophosphate and whether the N-terminal 1-34 peptide of bovine PTH is responsible for the lipolytic effect. Studies were also performed to determine if parathyroid extract (PTE) produces lipolysis in normal subjects and in patients with pseudohypoparathyroidism in whom there is a defect in the adenylate system in response to PTH in the renal cortex and presumably in the skeletal system as well. It was found that highly purified bovine PTH in the concentration range between 10(-9) M and 10(-5) M stimulated lipolysis in vitro by human fat in a dose-dependent manner. Significant increases in glycerol production were observed at concentrations of PTH as low as 10(-9) M and maximal increases were seen at 10(-6) M. The hormone significantly increased the concentration of cyclic adenosine 3' ,5'-monophosphate in fat tissue. The synthetic N-terminal 1-34 peptide of bovine PTH was as effective as the native hormone in stimulating glycerol production at a concentration of 10(-9) M-10(-6) M. PTE, 100 mU per kg per min for 30 min given intravenously, produced transient increases in the concentration of plasma free fatty acid in each of eight normal subjects, three patients with hypoparathyroidism and eight patients with pseudohypoparathyroidism. Purified bovine PTH also increased plasma free fatty acid in each of two normal subjects. It is concluded that PTH stimulates lipolysis in human subcutaneous fat, that this action of the hormone is mediated through cyclic adenosine 3', 5'-monophosphate and that the N-terminal 1-34 peptide portion of the hormone is responsible for this lipolytic action. Further, PTE stimulates lipolysis in vivo in man. There appears to be no defect in the adenylate cyclase system in the fat cell in response to PTH in patients with pseudohypoparathyroidism.

Adipose Tissue↗
PubMed1976

Demonstration that cyclic adenosine 3',5'-monophosphate mediates the lipolytic action of parathyroid hormone.

Studies were carried out with rat epididymal fat pads first to compare the effects of the synthetic N-terminal 1-34 peptide of bovine parathyroid hormone and of the native hormone to determine whether this portion of the molecule is responsible for the lipolytic action of the hormone and second to determine whether this biologic action of parathyroid hormone is mediated by cyclic adenosine 3',5'-monophosphate. The N-terminal polypeptide was as effective as the native hormone in stimulating lipolysis in the concentration range between 10(-8) M and 10(-6) M. Parathyroid hormone stimulated lipolysis by isolated fat cells. The concentration of cyclic adenosine 3',5'-monophosphate in the fat pads was significantly increased by the hormone (10(-6)M). Lipolytic stimulation by parathyroid hormone (10(-6)M) was diminished by insulin (100 muU/ml) and prostaglandin E1 (1 mug/ml), both of which are known inhibitors of lipolysis. The findings indicate that the amino-terminal 1-34 peptide portion of parathyroid hormone is responsible for the lipolytic action and that this effect is mediated through cyclic adenosine 3',5'-monophosphate.

Adipose Tissue↗
PubMed1976

Responsiveness to glucagon in fetal hearts. Species variability and apparent disparities between changes in beating, adenylate cyclase activation, and cyclic AMP concentration.

Previous studies of the ability of the immature heart to respond to glucagon have yielded conflicting results. To test the possibility that the apparent discrepancies might be explained in part by species variability, isolated hearts of fetal mice and rats (13-22 days' gestational age) were studied under identical conditions in vitro. Changes in atrial rate and ventricular contractility were measured in spontaneously beating hearts exposed to glucagon, and activation of adenylate cyclase was assayed in cardiac homogenates. In mice of 16 days' gestational age or less, there was no change in heart rate in response to glucagon; at 17-18 days, minimal responsiveness was present; and after 19 days, 10muM glucagon caused an increase in spontaneous atrial rate of 30 +/- 4% (SEM) (P less than 0.001). Measurement of the extent and speed of volume displacement of the isotonically contracting hearts with a specially constructed capacitance transducer revealed that ventricular inotropic responsiveness also appeared after 17-19 days. Cardiac stores of glycogen were reduced in older hearts exposed to glucagon, but not in those aged less than 16 days. In contrast, glucagon failed to activate adenylate cyclase in homogenates of hearts of fetal mice at any age. Furthermore, glucagon failed to elicit an increase in the concentration of cyclic AMP in spontaneously beating hearts that developed tachycardia. Responses in hearts of fetal rats were distinctly different from those in mouse hearts: at no age was there any change in heart rate, strength of contraction, glycogen content, or adenylate cyclase activation. Thus, there are major species differences in cardiac pharmacological maturation. Although the mouse heart develops the ability to increase its rate and strength of contraction and to undergo glycogenolysis in response to glucagon well before birth, the rat heart does not. In addition, there is an apparent disparity in late fetal mouse hearts between the ability of glucagon to induce functional responses and its ability to stimulate adenylate cyclase and increase cyclic AMP levels. It is impossible, of course, to rule out absolutely the possibility that localized increases in a critical cyclic AMP pool were present but too small to measure in the entire tissue. Nevertheless, the most obvious interpretation of our results is that they are compatible with the hypothesis that glucagon may exert some of its hemodynamic effects independently from the adenylate cyclase-cyclic AMP system in the late-fetal mouse heart.

Adenylyl Cyclases↗
PubMed1976

Effect of acetylcholine on glycogen phosphorylase activity and cyclic nucleotide content in isolated perfused rat hearts.

Acetylcholine (1muM) increased cyclid GMP content in paced perfused rat hearts within 15 sec., with peak content occurring at 1 min. No effect of acetylcholine on cyclic AMP content, phosphorylase activity or glycogen synthase was observed. Epinephrine (1muM) infusion increased both cyclic AMP content and phosphorylase, but did not alter cyclic GMP content or glycogen synthase activity. When acetylcholine was infused during the second min. of a 2 min. infusion of epinephrine, the cholinergic agent increased cyclic GMP and reduced the stimulated phosphorylase activity and elevated cyclic AMP.

Acetylcholine↗
PubMed1976

Regulation of cyclic nucleotide levels and glycogen phosphorylase activity by acetylcholine and epinephrine in perfused rat hearts.

Acetylcholine (ACh) produced a time and dose-dependent increase in cyclic 3',5'-guanosine monophosphate (cyclic GMP) levels in perfused rat hearts without any significant (P greater than .05) change in cyclic 3',5'-adensoine monophosphate (cyclic AMP) level or glycogen phosphorylase activity. Epinephrine produced a dose-dependent increase in both cyclin AMP and phosphorylase activity but no significant (P greater than .05) change in cyclic GMP levels. When ACh (10(-6) M) was infused into hearts during the infusion of epinephrine (10(-6) M), a time-dependent increase in cyclic GMP and decrease in cyclic AMP occurred, both of which preceded a significant (P less than .05) decrease in glycogen phosphorylase activity. In epinephrine-stimulated hearts, ACh produced a dose-dependent increase in cyclic GMP levels. Similar concentrations produced a fall in cyclic AMP levels and phosphorylase activity. No condition tested resulted in a significant (P greater than .05) change in glycogen synthase activity. It is concluded that ACh can reduce cyclic AMP levels and phosphorylase activity only when they have been elevated above basal values. These changes are associated with an increase in cyclic GMP. The reduction in phosphorylase produced by ACh may be the result of either or both of the changes in cyclic nucleotide levels.

Acetylcholine↗
PubMed1975

Effects of glucagon, phosphodiesterase inhibitors, and trypsin treatment on cyclic 3',5' adenosine monophosphate levels in isolated hepatocytes.

Cyclic 3',5' adenosine monophosphate (cyclic AMP) levels were measured in isolated hepatocytes under several conditions. Following the addition of glucagon cyclic AMP levels increased rapidly with peak values occurring at three minutes. The increase in cyclic AMP was dose dependent. Significant increases were found with 10(-10)M glucagon and a maximum increase of twenty fold was produced by 10(-8) M glucagon. This action of glucagon was augmented by the phosphodiesterase inhibitors, theophylline, SQ 20,009, and papaverine. Treatment of the hepatocytes with trypsin markedly reduced the response to glucagon.

Animals↗