USE OF FROZEN-SECTIONS FOR THE PHARMACOLOGICAL CHARACTERIZATION OF COMPOUNDS ACTIVE ON NEUROTRANSMITTER RECEPTORS

Radioligand binding assay represents an important technique in pharmac ological and pharmaceutical research for assessing the receptor profil e of new drugs or of compounds under development. In this study, the p harmacological profile and the receptor specificity of compounds activ e on dopamine and muscarinic cholinergic receptor subtypes were evalua ted using as a receptor source, membrane preparations or frozen sectio ns. Dopamine D-1-like receptors were assayed in membrane preparations or frozen sections of rat striatum and kidney with [H-3]SCH 23390 as a ligand. Rat striatum, kidney and atrium were used as a source of dopa mine D-2-like receptors with [H-3]-spiperone as a ligand. The non-sele ctive muscarinic cholinergic receptor antagonist [H-3]-N-methyl-scopol amine was used to label muscarinic cholinergic receptors in the rat. F rontal cortex represented the source of M-1 receptor subtype, heart th e source of M-2 receptor subtype, sub maxillary gland the source of M- 3 receptor subtype and striatum the source of M-4 receptor subtype. Wi th the exception of cardiac tissue, no significant differences were no ticeable in the affinity of dopaminergic or muscarinic cholinergic com pounds tested using membrane particles or 8 mu m thick slide-mounted s ection, In the heart, frozen sections gave lower dissociation constant and inhibition constant values than membranes. The above findings sug gest that radioligand binding assay on slide-mounted tissue sections m ay represent a suitable technique for assessing the receptor profile o f drugs under development for the treatment of disorders characterised by dopaminergic or muscarnic cholinergic dysfunction.