The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jun 1993
Speed of action of various muscle relaxants at the neuromuscular junction binding vs. buffering hypothesis.
The speed of action of several nondepolarizing muscle relaxants (gallamine, rocuronium, D-tubocurarine, atracurium, vecuronium, pancuronium and doxacurium) was tested iontophoretically at the frog cutaneous pectoris neuromuscular junction at various temperatures. If differences in rate of onset and offset are due to different molecular rates of binding (and unbinding), and of resulting conformational changes, they should be strongly temperature dependent. In contrast, if differences are due to differences in buffered diffusion, temperature dependence should be low to moderate. ⋯ Because KD values of all muscle relaxants were even less temperature dependent (Q10 < 1.3), this suggests that the kinetics of inhibition is probably determined by the extent of buffering in the synaptic cleft, and not by binding and unbinding. Diffusion of relaxants from the synaptic cleft is expected to be strongly buffered, because the nerve terminal presents a physical barrier to diffusion, and because of extremely high density of acetylcholine receptors. The density of acetylcholine receptors can be calculated from the time constant of offset and KD values of various relaxants, assuming that buffer diffusion is determining the kinetics of action of muscle relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)
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J. Pharmacol. Exp. Ther. · Jun 1993
Pulmonary thromboembolism-induced alterations in nitric oxide release from rat circulating neutrophils.
We have earlier reported that neutrophils play an important role in pulmonary thromboembolism. The effect of circulating polymorphonuclear leukocytes (PMNL) isolated from normal and thrombotic rats was, therefore, studied on platelet aggregation in platelet-rich plasma. PMNL inhibited the platelet aggregation in a concentration- and time-dependent manner at 37 degrees C. ⋯ These observations suggested that the inhibitory effect of PMNL on platelets was mediated by neutrophil-derived relaxing factor. PMNL, obtained after thromboembolism, inhibited the platelet aggregation response more strongly due to an increased release of nitric oxide from them. It is suggested that PMNL play an important role in the regulation of hemostasis.