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E Connolly

Publications and source records attributed to E Connolly.

33 records · Page 2Linked to original sources
PubMed1987

Distinction between mechanisms underlying alpha 1- and beta-adrenergic respiratory stimulation in brown fat cells.

Experimental conditions are described for selective alpha 1- and beta-adrenergic stimulation of the respiration of brown fat cells. The dual agonist norepinephrine was unsuitable as a selective alpha 1-agonist, since unacceptably high concentrations of propranolol were needed to abolish the beta-response. Phenylephrine at 50 microM, in the presence of 5 microM dl-propranolol, was shown to lead to a maximal, selective alpha 1-stimulation, whereas maximal, selective beta-stimulation was achieved with 1 microM isoproterenol in the presence of 5 microM prazosin. The mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) was able to further increase respiration that was already maximally alpha 1-stimulated, but when added before the alpha 1-stimulation, FCCP totally abolished the response. In contrast, FCCP had no effect on the beta-stimulated response. Similarly, oligomycin (an inhibitor of mitochondrial ATP synthesis) inhibited alpha 1-respiration but had a much smaller effect on beta-respiration. Ouabain (an inhibitor of the Na+-K+-ATPase) halved alpha 1-respiration but only induced a small inhibition of beta-respiration. It is concluded that only a small fraction of thermogenesis from beta-adrenergic processes is due to oxidative phosphorylation, whereas alpha 1-respiration is largely due to the oxygen cost of mitochondrial ATP synthesis, and a large fraction of this ATP is apparently used for the restoration of ion gradients.

Adipose Tissue, Brown↗
PubMed1986

Norepinephrine-induced Na+ influx in brown adipocytes is cyclic AMP-mediated.

To examine the involvement of Na+ ions in adrenergic responses in brown adipose tissue, a method is described for measuring Na+ influx into isolated brown adipocytes, using short (30 s) incubations with 22Na+, followed by a two-step centrifugation recovery procedure. Using this method, a clear norepinephrine-stimulated accumulation of intracellular 22Na+ was observed, which was enhanced by the addition of ouabain, was insensitive to amiloride (a Na+/H+ exchange blocker), and could not be mimicked by the total removal of oxygen from the incubation medium. The norepinephrine-stimulated Na+ influx was dose-dependent for the hormone with an EC50 of 250 nM, was blocked by the beta-antagonist propranolol but not by the alpha 1-antagonist prazosin, and could be induced by adrenergic agonists with the order of potency: isoproterenol greater than norepinephrine greater than phenylephrine, indicating a beta-receptor-mediated process. The Na+ influx was found to be cAMP-dependent since it could be induced by both theophylline (a phosphodiesterase inhibitor) and forskolin (an adenylate cyclase activator), but it was independent of other known cellular cAMP-dependent responses since neither addition of fatty acid substrates (octanoate or palmitate), nor of the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone could induce the phenomenon, despite having significant stimulatory effects on cellular respiration. Furthermore, total respiratory inhibition with rotenone, or total oxygen depletion of the medium with dithionite, did not prevent the normal norepinephrine-induced Na+ influx. The possibility that this beta-mediated norepinephrine-stimulated Na+ influx plays an important physiological role in brown adipose tissue activity is discussed, perhaps as one of the, as yet undefined, signals initiating tissue growth in the chronically beta-stimulated tissue of animals facing long-term increases in thermogenic demands.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Presence of a Ca2+-dependent K+ channel in brown adipocytes. Possible role in maintenance of alpha 1-adrenergic stimulation.

We have previously demonstrated mobilization of Ca2+ in and efflux of Rb+ (K+) from isolated hamster brown adipocytes as a consequence of norepinephrine stimulation. We have now investigated the adrenoceptor subtype specificity of these responses and found them both to be of the alpha 1-subtype. Further, we have found that the Rb+ (K+) efflux was dependent upon a primary Ca2+ mobilization event in response to the alpha 1-adrenergic stimulation, since the Rb+ efflux could also be demonstrated by the addition of the Ca2+ ionophore A23187 to the cells. The norepinephrine- and A23187-stimulated Rb+ effluxes were both inhibited by the Ca2+-dependent K+-channel blocker apamin. Apamin also significantly attenuated Ca2+ mobilization in cells in response to a submaximal concentration of norepinephrine. We conclude that alpha 1-adrenergic stimulation of brown fat cells leads to a mobilization of intracellular Ca2+ which, in itself or via other mechanisms, leads to an increase in cytosolic Ca2+ concentration which, in turn, activates a Ca2+-dependent K+ channel, leading to a K+ release from these cells. A possible role for this channel to sustain and augment the response to alpha 1-adrenergic stimulation is discussed.

Adipose Tissue, Brown↗
PubMed1984

Na+-dependent, alpha-adrenergic mobilization of intracellular (mitochondrial) Ca2+ in brown adipocytes.

The existence and significance of a hormone-sensitive, rapidly mobilizable intracellular pool of Ca2+ in hamster brown-fat cells was investigated with 45Ca2+-labelling techniques. It was shown that such a pool existed and was probably located within the abundant mitochondria. It was rapidly mobilized by norepinephrine (median effective concentration 50 nM) through alpha-adrenergic mechanisms. The mobilization of Ca2+ from the intracellular stores (mitochondria) required the presence of extracellular Na+, but not of Ca2+, K+ or Mg2+. It is concluded that the experiments are in agreement with a hypothesis linking the mobilization of intracellular Ca2+ pools with an alpha-adrenergically-induced increase in plasma membrane Na+ permeability (observed as a membrane depolarization), and a subsequent activation of the mitochondrial Na+/Ca2+ exchange, leading to mobilization of mitochondrial Ca2+ and the mediation of alpha-adrenergic effects as a result of an elevated cytosolic Ca2+ level.

Adipose Tissue, Brown↗
PubMed1984

Possible expression of the obese gene in the brown adipose tissue of lean heterozygote littermates of the genetically obese (ob/ob) mouse.

Lean littermates of the genetically obese (ob/ob) mouse of confirmed genotype, +/+ wildtype or ob/+ heterozygous, were fed either stock diet or a high-energy 'cafeteria' diet. Body weights food consumption, and weights and metabolic parameters of the interscapular and dorso-cervical brown adipose tissue sites were examined. Both genotypes showed similar characteristics of food intake and body weight gain on the cafeteria diet. The ob/+ brown adipose tissue was, however, different from the +/+ in that the GDP binding to the mitochondria was lower and the cytoplasmic density of the mitochondria in the tissue was higher in both stock and cafeteria fed groups. It is suggested that the decreased GDP binding is partly compensated for by an increase in the mitochondrial content of the brown adipose tissue of the ob/+ mice, thus normalizing the total thermogenic capacity and allowing the maintenance of lean body weight despite a slight expression of the obese gene in the thermogenic pathway.

Adipose Tissue, Brown↗
PubMed1983

Intraoperative neurosurgical ultrasound: transdural and transfontanelle applications.

High-resolution real-time ultrasound scanning of 54 patients was performed with a sector scanner during a variety of neurological procedures. Scans obtained at the time of craniotomy were successful in characterizing and localizing tumors, abscesses, arteriovenous malformations, and hematomas within the brain of 15 of 16 adult patients. One attempt to visualize a brain cyst through a 15-mm burr hole was unsuccessful. Scanning of 37 infants and young children was performed through the anterior fontanelle during placement of ventricular shunts. This allowed for the accurate placement of shunts in all patients and resulted in fewer short-term and long-term complications. Intraoperative ultrasound is a practical and highly effective means of providing intraoperative localization of intracranial anatomy and disease.

Brain Diseases↗
PubMed1982

Responses to cafeteria feeding in mice after the removal of interscapular brown adipose tissue.

Feeding a cafeteria diet to mice resulted in an increased energy intake of approximately 30% and this led to increases in the wet weight, total protein content, and total cytochrome oxidase activity of interscapular and dorso-cervical brown adipose tissue. Surgical removal of interscapular brown adipose tissue, followed by cafeteria feeding, gave rise to an elevation in dorso-cervical brown adipose tissue wet weight, total protein content, and total cytochrome oxidase activity, compared to intact cafeteria-fed mice. Cafeteria feeding with or without the removal of interscapular brown adipose tissue did not lead to significant increases in body weight compared to stock-fed control mice, but both cafeteria-fed groups of mice showed significant elevations in body fat content indicating that the induced hyperphagia led to a relative obesity in the cafeteria-fed groups. The results presented are consistent with an increased thermogenic activity in the brown adipose tissue of cafeteria-fed mice, and the effect of the removal of interscapular brown adipose tissue further indicates the quantitative importance of the tissue in the control of body weight.

Adipose Tissue, Brown↗
PubMed1982

The effect of interscapular brown adipose tissue removal on body-weight and cold response in the mouse.

1. The removal of the interscapular brown adipose tissue (IBAT) led to an increase in body-weight of normal, lean mice as compared to anaesthetized controls. 2. No significant difference in food consumption could be detected between the two groups of mice over the period of the experiment. 3. Fat extraction of the whole carcasses with chloroform:methanol showed a statistically significant increase in fat content in the animals without IBAT. 4. There was no apparent failure in the operated animals to sustain core temperature when exposed to a cold stress situation (4 degrees for 24 h). 5. There was no difference in the wet weight, protein content or cytochrome oxidase content of the dorso-cervical brown adipose tissue (DCBAT) between operated and control mice. This is indicative of a lack of proliferation of other brown adipose tissue sites in the operated mice in response to the removal of the IBAT. 6. It is suggested that brown adipose tissue is implicated in dietary thermogenesis in the mouse.

Adipose Tissue, Brown↗
PubMedDate not supplied

Professional partnerships in primary care practice.

Professional partnerships in pediatric primary care produce opportunities for blending nursing and medical roles to offer optimal health care to children and families. During the Sixth Annual Pediatric Nursing Conference, held October 4-7, 1990 in San Francisco, issues of role delineation, reimbursement or salary schedules, prescriptive authority, on-call status, malpractice coverage, and hospital privileges were discussed among a distinguished panel of PNPs and physicians.

Humans↗