A Cyclic Adenosine Monophosphate Link in the Catecholamine Enhancement of Transmitter Release at the Neuromuscular Junction

The frequency of miniature endplate potentials (mepps) in rat diaphragms was markedly increased by epinephrine and norepinephrine in preparations exposed to 15 mM K⁺. The effect was rapid in onset but gradually declined during continued exposure to the catecholamines. N⁶, O^2'-dibutyryl adenosine 3',5'-monophosphate (dibutyryl-cAMP) also caused transient frequency increases resembling in time-course those observed with catecholamines. Contrary to previous reports, catecholamines and dibutyryl-cAMP had little effect on mepp frequency in preparations not treated with K⁺. Sustained increases with theophylline and decreases with adenosine were found in both K⁺-treated and untreated preparations. Analysis of the data obtained with catecholamines showed the intensity of the response to be a function of nerve terminal polarization. The inability of catecholamines and dibutyryl-cAMP to affect mepp frequency of untreated preparations argues against an obligatory role for cAMP in the neurosecretory mechanism. The findings are consistent with an action of catecholamines and cAMP in the regulation of transmitter release at fatigued preparations.