Neurotransmitter modulation of prostaglandin E1-stimulated increases in cyclic AMP: II. Characterization of a cultured neuronal cell line treated with dibutyryl cyclic AMP

Abstract The ability of selected neurotransmitters to modulate PGE,-stimulated increases in cAMP was tested in the somatic cell hybrids TCX 17 and TCX 11 differentiated by growth in dibutyryl cAMP. PGE 1 was shown to cause an increase in cellular cAMP. Carbachol, noradrenaline and dopamine inhibited the effect of PGE 1 , while 5-hydroxytryptamine had no effect. The carbachol inhibition is mediated by a muscarinic receptor since nicotinic antagonists failed to block carbachol while scopolamine reversed its effect. The noradrenaline inhibition was reversed by the antagonists phenoxy-benzamine and phentolamine, but not by the β-antagonists propranolol and dichloroisoproterenol. The dopamine inhibition was reversed by chlorpromazine and trifluoperazine. The dopamine agonist ET495 mimicked dopamine while apomorphine had little or no effect. These results obtained from differentiated cells are compared to those reported for exponential growth phase cells of the same cell line. Distinct differences were found with respect to the pharmacology of the noradrenaline and dopamine inhibition. Finally, the biochemical results are compared to the electrophysiological results reported for the cell lines. Neurotransmitter agents that modulate PGE, effects do not necessarily elicit membrane conductance changes, and, similarly, neurotransmitters that elicit an electrophysiological response do not inhibit PGE 1 -stimulated increases in cAMP. Dopamine elicits an electrophysiological response and inhibits the effects of PGE 1 . The possibility exists that a single receptor is mediating two cellular events.