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Biomedical subjects

J J Singer

Publications and source records attributed to J J Singer.

60 records · Page 4Linked to original sources

Evidence for a role of cyclic AMP in neuromuscular transmission.

Experiments were undertaken to determine if the effects of epinephrine in promoting neuromuscular transmission were mediated by adenosine 3':5'-cyclic phosphate (cyclic AMP). Dibutyryl cyclic AMP and the methyl xanthines, theophylline and caffeine (which inhibit cyclic AMP hydrolysis), were found to increase the amplitude of the end plate potential in the isolated rat diaphragm. Like epinephrine (which is known to promote cyclic AMP synthesis), these agents appear to facilitate the release of acetylcholine from the motor neuron. This interpretation is supported by the observation that theophylline and dibutyryl cyclic AMP markedly increased the frequency but not the amplitude of the spontaneous miniature end plate potentials. In addition, these drugs increased the number of transmitter packets released in response to nerve stimulation. These results are consistent with the view that cyclic AMP plays a role in the release of acetylcholine and in the "defatiguing effect" of epinephrine.

Acetylcholine↗

Direct effects of fatty acids and other charged lipids on ion channel activity in smooth muscle cells.

A variety of fatty acids increase the activity of certain types of K+ channels. This effect is not dependent on the three enzymatic pathways that convert arachidonic acid to various bioactive oxygenated metabolites. One type of K+ channel in toad stomach smooth muscle cell membranes in activated by fatty acids and other single chain lipids which possess both a negatively charged head group and a sufficiently hydrophobic acyl chain. Neutral lipids have no effect on K+ channel activity, while positively charged lipids with a sufficiently hydrophobic acyl chain suppress channel activity. Acyl Coenzyme A's, which do not flip across the bilayer, act only from the cytosolic surface of the membrane, suggesting that the binding site for channel activation is also located there. This fatty acid-activated channel is also activated by membrane stretch. Moreover, this mechanical response is either mediated or modulated by fatty acids. Thus, fatty acids and other charged single chain lipids may comprise another class of first or second messenger molecules that target ion channels.

Acyl Coenzyme A↗