Effects of several ergosines on adenylate cyclase activity in synaptosomal membranes of the bovine caudate nucleus.

The effects of several ergosines and different dopamine agonists and antagonists on the activity of dopamine-sensitive adenylate cyclase in synaptosomal membranes of the bovine caudate nucleus were comparatively studied. Among ergot alkaloid derivatives used, ergosinine was the most active in stimulating adenylate cyclase activity. Ergosine, bromoergosine, dihydroergosine, dihydroergocryptine and lisuride also stimulated this enzyme. Dihydroergosinine, bromodihydroergosine and bromoergocryptine did not affect adenylate cyclase activity. Saccharino derivatives of both ergosine and ergosinine were inactive. When used in higher concentrations, ergosine, ergosinine, dihydroergocryptine and lisuride inhibited dopamine-stimulated adenylate cyclase whereas other ergot alkaloid derivatives examined did not. If the extent of dopamine-sensitive adenylate cyclase stimulation is considered as a measure of dopaminergic activity, examination of the structure/dopaminergic activity relationship showed that modifications of ergot alkaloid molecules such as isomerization in position 8, hydrogenation of delta 9(10)-double bond, or introduction of bromine into position 2 of the molecule, lead to a significant decrease of stimulatory effects of adenylate cyclase. Introduction of a saccharino group into position 2 of the molecule caused a total loss of stimulatory activity of both ergosine and ergosinine, probably because of the size of the saccharino residue.