Characterization of homologous 5-hydroxytryptamine sub(4) receptor desensitization in colliculi neurons

Exposure of mouse colliculi neurons to selective 5-hydroxytryptamine (5-HT) sub(4) agonists was accompanied by a rapid desensitization of the receptor-stimulated adenylyl cyclase response. Half-maximal desensitization occurred after 2 min. Only exposure of neurons to selective 5-HT sub(4) agonists led to a potent desensitization of the 5-HT sub(4)-mediated response. Neurons exposed to other agents, like isoproterenol, vasoactive intestinal peptide, or forskolin, that increase cAMP levels did not undergo any desensitization of 5-HT sub(4) receptors. Activation of protein kinase A with either 8-bromo-cAMP or dibutyryl-cAMP or application of inhibitors of protein kinase A-dependent phosphorylation did not change the rate of 5-HT sub(4)-induced desensitization. No shift to lower potency of 5-HT sub(4) agonists in the concentration-response curve was observed. These results suggest that 5-HT sub(4) receptor agonists induced homologous but not cAMP-mediated heterologous desensitization.