A selective inhibitor of cAMP‐specific phosphodiesterase, Ro 20–1724, has no effect on the quantal release of acetylcholine from the mouse phrenic nerve

Abstract— The indirect twitch response of the mouse isolated phrenic nerve‐diaphragm preparation, partially paralysed by tubocurarine, was restored only by about 10% by Ro 20–1724 at 2 to 280 μM. The solvent vehicle, dimethylsulphoxide, also showed the same effect to a similar extent. Intracellular recordings with glass microelectrodes revealed that Ro 20–1724 (40 μM) affected neither the resting membrane potential, the amplitude and frequency of miniature endplate potentials nor the amplitude of nerve‐impulse evoked endplate potentials recorded in curarized preparations. The result indicates that Ro 20–1724 at a concentration four times the IC50 of phosphodiesterase inhibition has no effect on the quantal release of acetylcholine from a mammalian motor nerve and suggests that cAMP has no modulatory effect on the transmitter release.

[1]  S. Vogel,et al.  The effects of an adenylate cyclase inhibitor on the electrophysiological correlates of neuromuscular transmission in the frog , 1986, British journal of pharmacology.

[2]  H. Meiri,et al.  The fusogenic substance dimethyl sulfoxide enhances exocytosis in motor nerve endings. , 1985, Biochimica et biophysica acta.

[3]  K. Dretchen,et al.  Physostigmine inhibition of 3',5'-cyclic AMP phosphodiesterase from cat sciatic nerve. , 1984, The Journal of pharmacology and experimental therapeutics.

[4]  J. Häggblad,et al.  Release of acetylcholine at the motor endplate of the rat — evidence against a muscarinic acetylcholine autoreceptor , 1983, British journal of pharmacology.

[5]  K. Dretchen,et al.  Cyclic Nucleotides in Neuromuscular Transmission , 1981, Anesthesia and analgesia.

[6]  R. Jacobs,et al.  Motor nerve terminal facilitatory action of SQ 20009: an inhibitor of cyclic nucleotide phosphodiesterase. , 1977, The Journal of pharmacology and experimental therapeutics.

[7]  L. Skirboll,et al.  A role of cyclic nucleotides in neuromuscular transmission. , 1976, The Journal of pharmacology and experimental therapeutics.

[8]  K. Prasad,et al.  Differences and Similarities Between Guanosine 3′,5′-Cyclic Monophosphate Phosphodiesterase and Adenosine 3′, 5′-Cyclic Monophosphate Phosphodiesterase Activities in Neuroblastoma Cells in Culture , 1975, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[9]  D. Wilson The effects of dibutyryl cyclic adenosine 3',5'-monophosphate, theophylline and aminophylline on neuromuscular transmission in the rat. , 1974, The Journal of pharmacology and experimental therapeutics.

[10]  R. Jacobs,et al.  Facilitatory sites of action of theophylline in isolated cat tenuissimus muscle. , 1973, Neuropharmacology.

[11]  B. L. Ginsborg,et al.  The effect of adenosine on the release of the transmitter from the phrenic nerve of the rat , 1972, The Journal of physiology.

[12]  I. G. Marshall,et al.  Some actions of dimethylsulphoxide at the neuromuscular junction , 1972, The Journal of pharmacy and pharmacology.

[13]  J. J. Bray,et al.  Adenyl cyclase, cyclic nucleotide phosphodiesterase and axoplasmic flow. , 1971, Brain research.

[14]  A. L. Goldberg,et al.  Evidence for a role of cyclic AMP in neuromuscular transmission. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[15]  P. Gage The effect of methyl, ethyl and n-propyl alcohol on neuromuscular transmission in the rat. , 1965, The Journal of pharmacology and experimental therapeutics.

[16]  S. Hong,et al.  Does endogenous adenosine modulate the release of acetylcholine from motor nerve during single and repetitive stimulations in the mouse diaphragm? , 1987, Japanese journal of pharmacology.

[17]  E. M. Silinsky On the mechanism by which adenosine receptor activation inhibits the release of acetylcholine from motor nerve endings. , 1984, The Journal of physiology.

[18]  C. Briggs,et al.  Proving a role for cyclic AMP in synaptic transmission , 1982 .

[19]  A. Schurmann,et al.  Effects of antiallergic agents, compound 48/80, and some reference inhibitors on the activity of partially purified human lung tissue adenosine cyclic 3',5'-monophosphate and guanosine cyclic 3',5'-monophosphate phosphodiesterases. , 1977, Molecular pharmacology.