Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylate cyclase activity is lower in membrane preparations of fat cell homogenates from exercise-trained compared with sedentary rats (J. Appl. Physiol.: Respirat. Environ, Exercise Physiol. 42: 884-888, 1977). In the present investigations lipolysis and cyclic adenosine 3':5'-monophosphate (cAMP) accumulation were measured in isolated parametrial fat cells prepared from sedentary and trained rats. The purpose of these investigations was to determine whether the normal catecholamine-induced increases in cAMP accumulation is affected in isolated adipocytes from endurance-trained rats. The increases in cAMP accumulation in response to isoproterenol (0.01-10 microM) was reduced in fat cells isolated from trained rats. However, glycerol release in response to the same hormonal challenge was greater in these adipocytes. cAMP phosphodiesterase activity measured at 0.125 and 1.025 microM cAMP was greater in the particulate fraction of fat cell homogenates obtained from trained rats as compared with their sedentary counterparts. Hormone-sensitive lipase activity was reduced in crude fat pad homogenate preparations from trained rats if the animals were killed at rest. However, if the animals were run to exhaustion immediately prior to being killed, there were no differences in the hormone-sensitive lipase activity between preparations from trained and nontrained rats. These data indicate that, although cAMP accumulation by isolated fat cells in response to isoproterenol is markedly lower in trained rats, lipolysis and hormone-sensitive lipase activation is not reduced.
 ...
PMID:Lipolysis and cAMP accumulation in adipocytes in response to physical training. 625 98

Papaverine, despite being a potent phosphodiesterase inhibitor, actually blocks adipocyte lipolysis. The present study was designed to clarify the mechanism of the inhibitory effect of papaverine on lipolysis. Lipolysis, stimulated by either 10 microM isoproterenol or 5 mM dibutyryl cAMP, was significantly inhibited by papaverine (100 microM and above). Papaverine, however, did not affect the isoproterenol-induced increase in the protein kinase A (A-kinase) activity ratio. In cell-free extract from non-stimulated adipocytes, cAMP-stimulated A-kinase activities were almost completely blocked by H-89, a potent inhibitor of A-kinase, but not by papaverine. Thus, the inhibitory effect of papaverine on lipolysis could be responsible for a deficit in step(s) distal to A-kinase activity. Hormone-sensitive lipase activities in the infranatant fraction of centrifuged homogenates of cells, which were maximally stimulated with isoproterenol were significantly reduced. This result indicates that hormone-sensitive lipase redistributes from cytosol to its substrate in lipolytically stimulated cells. Papaverine completely blocked the isoproterenol-induced decrease in lipase activity in the infranatant fraction. These results suggest that papaverine blocks lipolysis through its inhibitory effect on the redistribution of hormone-sensitive lipase.
 ...
PMID:Inhibition of adipocyte lipolysis by papaverine: papaverine can inhibit the redistribution of hormone-sensitive lipase. 1089 95

Adipose tissue plays an important role providing energy to other tissues and functioning as an energy reserve organ. The energy supply is produced by triglycerides stored in a large vacuole representing approximately 95% of adipocyte volume. In the fasting period, triglyceride hydrolysis produces glycerol and free fatty acids which are important oxidative fuels for other tissues such as liver, skeletal muscle, kidney and myocardium. Hormone-sensitive lipase (HSL) is the enzyme that hydrolyzes intracellular triacylglycerol and diacylglycerol, and is one of the key molecules controlling lipolysis. Hormones and physiological factors such as dieting, physical exercise and ageing regulate intensively the release of glycerol and free fatty acids from adipocytes. One of the best known mechanisms that activate lipolysis in the adipocyte is the cAMP dependent pathway. cAMP production is modulated by hormone receptors coupled to Gs/Gi family of GTP binding proteins, such as beta-adrenergic receptors, whereas cAMP degradation is controlled by modulation of phosphodiesterase activity, increased by insulin receptor signalling. cAMP activates PKA which activates HSL by promoting its phosphorylation. Hormonal control of lipolysis can also be achieved by receptors coupled G proteins of the Gq family, through molecular mechanisms that involve PKC and MAPK, which are currently under investigation. cGMP and PKG have also been found to activate lipolysis in adipocytes. In this review we have compiled data from literature reporting both the classical and the alternative mechanisms of lipolysis.
 ...
PMID:Signalling mechanisms regulating lipolysis. 1618 14