Stimulation of phospholipase D by ADP-ribosylation factor.
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1,2-Dipalmitoylphosphatidylcholine↗
Biomedical subjects
H A Brown
Publications and source records attributed to H A Brown.
ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity.
The hydrolysis of phosphatidylcholine by phospholipase D (PLD) results in the production of phosphatidic acid and choline. An assay that uses an exogenous substrate was developed to measure this activity in membranes and solubilized preparations from HL60 cells. A cytosolic factor markedly enhanced PLD activity in membranes and was essential for GTP gamma S-dependent stimulation of an enriched preparation of PLD. The factor was purified to homogeneity from bovine brain cytosol and identified as a member of the ADP-Ribosylation Factor (ARF) subfamily of small G proteins. Subsequently, recombinant myristoylated ARF1 was found to be a better activator of PLD activity than was the nonmyristoylated form. ARF proteins have been implicated recently as factors for regulation of intracellular vesicle traffic. The current finding suggests that PLD activity plays a prominent role in the action of ARF and that ARF may be a key component in the generation of second messengers via phospholipase D.
ADP-Ribosylation Factor 1↗
Evidence that UTP and ATP regulate phospholipase C through a common extracellular 5'-nucleotide receptor in human airway epithelial cells.
Extracellular ATP and UTP produced a rapid accumulation of inositol phosphates in human airway epithelial cells (CF/T43). The order of agonist potencies for a series of nucleotide analogues differed markedly from that of the classically described P2x- or P2y-purinergic receptors. UTP was the most potent agonist and was fully efficacious; ATP and adenosine-5'-O-(3-thiotriphosphate) were also full agonists. In contrast, 2-methylthio-ATP, adenosine-5'-O-(2-thiodiphosphate) and alpha,beta-methylene-ATP were without effect. ADP and UDP had little or no effect at concentrations as high as 100 microM, and deoxyribose and dideoxyribose compounds were inactive. The effects of ATP and UTP were not additive, whereas bradykinin- or histamine-stimulated inositol phosphate production was additive with the effects of ATP or UTP. Preincubation of cells with either UTP or ATP resulted in a parallel loss of responsiveness to both agonists. Desensitization was specific for the response to nucleotides, because no ATP- or UTP-induced effect on the response to histamine or bradykinin was observed. Pertussis toxin treatment of CF/T43 cells produced a 30-40% decrease in the response to ATP or UTP, which correlated with the ADP-ribosylation of 41- and 43-kDa proteins. Bradykinin and histamine responses were not modified by pertussis toxin. Guanine nucleotides had little effect on the inositol phosphate response in intact CF/T43 cells at concentrations below 100 microM. However, in streptolysin-O-permeabilized cells GTP-gamma S produced a concentration-dependence activation of inositol phosphate formation. UTP or ATP had little effect in permeabilized cells in the absence of guanine nucleotides but markedly increased inositol phosphate formation in the presence of guanine nucleotides. Taken together, these results suggest that UTP and ATP activate a 5'-nucleotide receptor on CF/T43 cells that is distinct from the classically defined P2x- and P2y-purinergic receptors. Activation of phospholipase C by this receptor involves, at least in part, a guanine nucleotide-binding regulatory protein.
Adenosine Triphosphate↗
Temperature, thyroxine, and induced metamorphosis in tadpoles of a primitive frog, Ascaphus truei.
To understand the environmental factors and endocrine mechanisms which regulate the extended period (2 to 4 years) of larval development in Ascaphus, the effect of temperature and thyroxine (T4 by immersion) on metamorphic changes of the tail, limb buds, operculum, anal fold, oral disc, and teeth were studied in premetamorphic and prometamorphic tadpoles. (1) Control tadpoles did not undergo metamorphic change at any of the temperatures tested. (2) When tadpoles were kept in thyroxine solutions at 5 degrees, there were no changes in developmental morphology, and tadpoles kept at 18 and 20 degrees showed significant metamorphic changes in 5 to 6 days, but there was a high mortality at the higher T4 concentrations. The optimum temperature is about 10 degrees, and significant changes were completed in 3 weeks. (3) The premetamorphic tadpoles were less sensitive to T4 than prometamorphic tadpoles. The most responsive tissues are teeth and operculum, and the tail tissue shows the lowest sensitivity. (4) Duration of exposure to hormone and concentration also affect the growth or regression of larval tissue.
Animals↗
Type A behavior, personality, and sympathetic response.
This study examined, under two types of stress and during a typical workday, the moderating effects of the personality trait dependence/independence on the hemodynamic and catecholaminergic response in Type A individuals. During the mental stressor, Type As with strong dependency needs showed elevated heart rates and higher levels of epinephrine. During the physical stressor, they showed elevated heart rates and higher levels of norepinephrine. During the typical workday, both urinary catecholamines and mean daily heart rates were higher. It is suggested that these findings, which indicate greater sympathetic-adrenal response, are the result of a basic personality/behavior inconsistency and that Type A behavior may have an accentuated relationship to coronary disease when overlaid on a personality for which it is inconsistent.
Adult↗
Biochemical properties of a P2Y-purinergic receptor.
The turkey erythrocyte has substantial value as a model for the study of a receptor that exhibits pharmacological properties very similar to those delineated in mammalian tissues for a P2Y-purinergic receptor. The G protein-dependent coupling of this receptor to phospholipase C can be studied in detail, and the availability of an abundant source of homogeneous cells from which highly purified plasma membranes can be prepared, has led to the development of a radiolabeled, reversibly binding radioligand for a P2Y-purinergic receptor and a photoaffinity covalent radiolabel for this receptor. This source of plasma membranes highly enriched in P2Y-purinergic receptors should also serve as a rich starting material for the eventual purification and structural characterization of this important signaling protein.
Adenosine Triphosphate↗
Effect of duodenal ulcerogens cysteamine, mepirizole, and MPTP on duodenal myoelectric activity in rats.
Increased gastric acid secretion, enhanced acid delivery to the duodenum, and reduced alkaline secretion in the proximal duodenum are relatively well-established pathophysiologic abnormalities in duodenal ulcer. Impaired duodenal motility, however, may also contribute to duodenal ulceration by altering the distribution of acid and alkaline secretions along the upper digestive tract. We tested the hypothesis that the duodenal ulcerogens cysteamine, MPTP, and mepirizole modify duodenal motility in the rat and that motility changes might be a common and early alteration in experimental duodenal ulceration. All three duodenal ulcerogens rapidly produced extensive changes in duodenal myoelectric activity and reduced the frequency of myoelectric slow waves. Cysteamine induced marked hypermotility for at least 6 hr; MPTP rapidly decreased motility and fragmented the myoelectric migrating pattern. Mepirizole induced biphasic changes: an early hypermotility phase of about 30 min was followed by profound hypomotility. These results indicate that marked alterations of duodenal motility are common during experimental duodenal ulceration. In light of the differential effect of the ulcerogens on duodenal motility, it remains to be determined how these changes influence acid neutralization in the proximal duodenum. Nevertheless, our results suggest that all three duodenal ulcerogens, which are different in structure, alter duodenal motility.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Improving maternal health from the board room.
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Adult↗
Resolutions of the Aerospace Medical Association from 1929-41: Part II--1934-36.
The resolutions of the Aerospace Medical Association (formerly the Aero Medical Association of the United States) have been obtained and reviewed in detail for the period 1929-41. They provide a perspective on what Association members considered priority matters during the period. The resolutions cover subjects such as pilot fatigue, aviation medical examiner selection, military flight pay for flight surgeons, and other important issues, including medical standards. These resolutions had a significant impact during the early growth of civil aviation, and a number still influence today's aeromedical practice as well as certain flight operations.
Aerospace Medicine↗
Resolutions of the Aerospace Medical Association from 1929-41: Part III--1937-41.
The resolutions of The Aerospace Medical Association (formerly the Aero Medical Association of the United States) have been obtained and reviewed in detail for the period 1929-41. They provide a perspective on what Association members considered priority matters during that period. The resolutions cover subjects such as pilot fatigue, aviation medical examiner selection, military flight pay for flight surgeons, and other important issues, including medical standards. These resolutions had a significant impact during the early growth of civil aviation, and a number still influence today's aeromedical practice as well as certain flight operations.
Aerospace Medicine↗
Resolutions of the Aerospace Medical Association from 1929-41: Part I. 1929-33.
The resolutions of the Aerospace Medical Association (formerly the Aero Medical Association of the United States) have been obtained and reviewed in detail for the period 1929-41. They provide a perspective on what Association members considered priority matters during that period. The resolutions cover subjects such as pilot fatigue, aviation medical examiner selection, military flight pay for flight surgeons, and other important issues, including medical standards. These resolutions had a significant impact during the early growth of civil aviation, and a number still influence today's aeromedical practice as well as certain flight operations.
Aerospace Medicine↗
Effects of amnesic doses of reserpine or syrosingopine on mouse brain acetylcholine levels.
The effects of reserpine and syrosingopine on mouse whole brain acetylcholine levels were examined. At 2 or 24 hr following injection, the brains were removed and analyzed by mass spectrometry. No differences were found between drug-treated and control mice in the acetylcholine content of the brain at either time interval. The results suggest that whole brain acetylcholine levels do not predict the amnesic effects of either reserpine or syrosingopine.
Acetylcholine↗
In vitro effect of Panax ginseng on phytohaemagglutinin-induced lymphocyte transformation.
The effect of hydrocortisone or Panax ginseng, and/or a combination of hydrocortisone and Panax ginseng on phytohaemagglutinin (PHA-P)-induced transformation of peripheral blood lymphocytes were studied in 4 normal healthy adult volunteers. Increasing concentrations of Panax ginseng 0.16-1.60 micrograms X ml-1 caused a dose-related inhibition of PHA-P transformation of lymphocytes. A combination of 500 micrograms X ml-1 hydrocortisone and 0.80 micrograms X ml-1 Panax ginseng produced a greater suppression of PHA-P stimulation than either drug used alone. This suggests that Panax ginseng has a steroid-like effect in vitro, and may have a potentiating effect with hydrocortisone on T-cell-mediated immunity.
Adult↗
A method for isolation and culture of lymphocytes from endoscopic biopsies.
Human small and large intestinal lamina propria lymphocytes have been successfully prepared from endoscopic biopsies by a combined enzymatic and mechanical method which gives higher yields of viable mucosal lymphocytes than previously reported, despite the small size of the biopsy samples. Viability of the cells was demonstrated by dye exclusion and they could be satisfactorily maintained in short-term culture. Phytohaemagglutinin-P (PHA-P) transformation characteristics of intestinal lymphoid cells and those of peripheral blood were studied in 20 patients with Crohn's disease and 10 control subjects. Peripheral blood lymphocytes were separated according to this technique, no decrease in viability being observed when compared to a standard Ficoll-Hypaque gradient technique. Endoscopically abnormal (EA) and endoscopically normal (EN) Crohn's tissue showed significantly different responses to PHA-P (P less than 0.001), EA tissue lymphocytes giving lower blastogenic responses.
Adolescent↗
Effect of ginseng saponins and hydrocortisone on phytohemagglutinin transformation of lymphocytes.
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Adult↗
Embryonic temperature adaptations of the Pacific treefrog, Hyla regilla.
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Adaptation, Physiological↗
Temperature and development of the tailed frog, Ascaphus truei.
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Animals↗