Alteration of the acetylcholine response by intra- and extracellular serotonin application in intracellularly perfused neurons of Lymnaea stagnalis.

1. The effect of serotonin on the acetylcholine (ACh) response has been studied by means of voltage clamp and intracellular perfusion in unidentified isolated neurons from parietal and visceral ganglia of Lymnaea stagnalis. 2. In most cells studied serotonin added to the internal or external solution decreases the response to ACh. 3. In other neurons serotonin added to the intracellular solution increases the response to ACh; when it is added extracellularly it produces the opposite effect on the same cells. 4. The decreasing effect of serotonin on ACh currents is mimicked by cyproheptadine, an antagonist of serotonin receptors, and by the intracellular application of cyclic AMP (cAMP) forskolin. 5. The enhancing effect of intracellularly applied serotonin on ACh currents is blocked by cyproheptadine and is not obtained by the intracellular administration of cAMP and forskolin. In some cells the enhancing effect of serotonin appears after forskolin. 6. The results suggest a modulating effect of serotonin on cholinergic synaptic transmission in the nervous system of mollusks. The possible existence of intracellular serotonin receptors is discussed.

Intracellular injection of dopamine enhances acetylcholine responses of neuron R2 in the Aplysia abdominal ganglion.

1. At different levels of the holding potential on neuron R2 membrane in the Aplysia depilans abdominal ganglion, dopamine injected intracellularly increases the amplitude of both inward and outward currents recorded in response to the application of acetylcholine (ACh) to the ganglion surface. 2. The addition of dopamine to the external perfused solution produces generation of inward currents and a decrease in the cell response to the ACh. 3. The enhancing effect of injected dopamine on ACh responses is retained after inhibition of acetylcholinesterase (AChE) by a specific organophosphorous inhibitor, compound Gd-42. 4. The modulating effect of injected dopamine on ACh responses is discussed in terms of the existence of intracellular receptors of neurotransmitters in the differentiated cells.

Modulatory effect of serotonin on the acetylcholine sensitivity of identified neurons in the brain of Helix pomatia L.

Excitatory effect of acetylcholine (ACh) was modified by serotonin (5-HT) on identified neurons of intact brain with partially preserved functional connections at Helix pomatia L. Depolarization caused by ACh on neuron LPa3 and on several spontaneously active cells of the visceral ganglion was enhanced by brief application of 5-HT to the soma of these neurons. Guanosine triphosphate (GTP) and theophylline caused similar effects to the serotonin changes in ACh sensitivity of these cells. ACh sensitivity of neurons RPa3 and RPa2 was reduced following application of 5-HT, GTP and theophylline. Similarly, the effect of 5-HT tactile stimulation of the heart caused decrease in ACh sensitivity of neuron RPa2.

Interaction between acetylcholine and other agonists at cholinoreceptive membrane of mollusc neurons.

The effect of pretreatment with agonists of various chemical structure on acetylcholine action at isolated Limnaea stagnalis neurones was studied. Threshold concentrations of monoquaternary agonists or dicholinic ester of adipinic acid increase and inhibit the responses to low and high acetylcholine concentrations respectively. In contrast, suberyldicholine and compound IEM-1054 (containing two charged ammonium groups in a molecule with an internitrogen distance of 2.0-2.2 nm) decrease the action of any acetylcholine concentration. The results are discussed in terms of the cooperativity model of acetylcholine receptors (AChR) and the hypothesis about regular arrangement of AChRs in the membrane, the so called 'C-16 structure'.