cAMP-mediated decrease in K+ conductance evoked by serotonin and dopamine in the same neuron: a biochemical and physiological single-cell study.

Abstract
The extracellular application of either serotonin [5-hydroxytryptamine, 5-HT] or dopamine and the intracellular injection of cAMP all evoke in the same identified neurons of the snail Helix aspersa inward currents associated with a decrease in K+ conductance. The 5-HT-, dopamine- and cAMP-induced inward currents all show the same maximal amplitude. When the response to 1 transmitter is maximal, the response to the other is blocked. Using a single-cell microassay, both 5-HT and dopamine stimulate the adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of the neurons giving the inward-current responses. The adenylate cyclase activity of a neuron that does not show the 5-HT- and dopamine-induced currents was not stimulated by the transmitters. In contrast with the nonsummation of the maximal inward-current responses, the maximal stimulating effects of the transmitters on the enzyme activity are additive. The diterpene forskolin, which stimulates the adenylate cyclase activity of the single cells 9-fold, also evokes an inward current. Single snail neurons are endowed with independent 5-HT and dopamine receptors linked to the adenylate cyclase. Activation of each of these receptors evokes a cAMP-mediated decrease in K+ conductance. The physiological interaction between the transmitters probably takes place at a late step in the chain of events leading from the increase in cAMP to the closing of the K+ channels.