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Gamma-butylactone (GBL), a drug depressing the central nervous system, produced marked increases in acetylcholine contents in rat brain hemispheric regions (striatum, hippocampus, cortex) and in striatal choline content without modifying choline acetyltransferase or acetylcholinesterase activities. In the hippocampus GBL also strongly decreased the acetylcholine turnover rate and inhibited the high affinity uptake of choline. Its increase in acetylcholine content was prevented by an acute electrolytic lesion of the medial septum but not by a wide array of drug treatments designed to interfere with neurotransmission in various pathways. The results are taken to indicate that GBL directly depresses the cholinergic septal-hippocampal afferents by interrupting impulse flow. In the striatum, too, GBL markedly depressed the acetylcholine synthesis rate but had no effect on the high affinity choline uptake process. Such dissociation of the two phenomena had previously been observed using other drugs and may denote that acetylcholine synthesis in this region is regulated differently from that in the hippocampus. By comparison, gamma-hydroxybutyric acid (GHBA), an active metabolite which shares with GBL the capacity to produce a somnolent state and depress impulse flow in the dopaminergic nigroneostriatal pathway, had no effect on either striatal acetylcholine content or on hippocampal high affinity choline uptake. The results suggest that GBL can be distinguished from GHBA in its neuropharmacological central cholinergic effects.

No abstract

Platelet activation by the stable endoperoxide analogue U46619 is mediated largely by ADP released from platelet-dense granules. Polymorphonuclear leukocytes (PMNs) endowed with ecto-ADPase activity may operate as antiaggregatory cells in platelet aggregation induced by U46619. Unstimulated PMNs were effective in reducing aggregation when platelets were stimulated by threshold concentrations of U46619, whereas at higher concentrations of the stimulus, PMN activation is required. Evidence that the inhibition was mediated by PMN ecto-ADPase activity was obtained by high-performance liquid chromatography analysis, indicating that PMNs were able to efficiently metabolize platelet-active ADP into AMP. Moreover, PMN-derived supernatants were able to inhibit platelet aggregation, suggesting that under this circumstance the inhibition was exerted by an uncharacterized, releasable ADPase activity. This study supports the hypothesis that, besides nitric oxide and hydrogen peroxide, ADPase activity may represent another PMN-mediated pathway capable of regulating platelet activity in areas of reduced blood flow, such as those found in conditions of myocardial ischemia.

No abstract