Cyclic guanosine 3', 5'-monophosphate : studies on synthesis and efflux from hepatocytes, liver slices and cerebellar slices and on serotonin-mediated cGMP synthesis in human platelets

Abstract: The present study established the existence of a carrier mediated transport of 3'5' cGMP from rat liver slices, hepatocytes and cerebellar slices in which the cellular levels of 3'5' cGMP were elevated by application of appropriate stimuli and inhibitors of the 3'5' cyclic nucleotide phosphodiesterase. The carrier is specific for 3'5' cGMP as opposed to 3'5' cAMP. The temperature dependent transport is inhibited by probenecid, a known inhibitor of anion transport with IC50 value of 0.5 itiM. Alkylating reagents increase the rate of transport implying the participation of some protein.The molecular mechanism of the 5HT-mediated 5-10 fold increase in 3'5' cGMP levels in human platelets, which unlike other neurotransmitter mediated increases in 3'5' cGMP did not depend on the presence of extracellular Ca++, was investigated. On the basis of the Na+ and Cl- dependence of cGMP response it was concluded that the uptake of 5HT is an obligatory step in stimulation of the synthesis of 3'5' cGMP. Inhibition of the 5HT-mediated increase in 3'5' cGMP by 5HT uptake blocking antidepressant drugs but not by antagonists of 5HT-type 1 or type 2 receptors corroborates this conclusion.The 5HT-mediated increase in 3'5' cGMP has been studied in platelets from depressed patients during the course of electroconvulsive treatment.