Use of frozen sections for the pharmacological characterization of compounds active on neurotransmitter receptors.
Radioligand binding assay represents an important technique in pharmacological and pharmaceutical research for assessing the receptor profile of new drugs or of compounds under development. In this study, the pharmacological profile and the receptor specificity of compounds active on dopamine and muscarinic cholinergic receptor subtypes were evaluated using as a receptor source, membrane preparations or frozen sections. Dopamine D1-like receptors were assayed in membrane preparations or frozen sections of rat striatum and kidney with [3H]-SCH 23390 as a ligand. Rat striatum, kidney and atrium were used as a source of dopamine D2-like receptors with [3H]-spiperone as a ligand. The non-selective muscarinic cholinergic receptor antagonist [3H]-N-methyl-scopolamine was used to label muscarinic cholinergic receptors in the rat. Frontal cortex represented the source of M1 receptor subtype, heart the source of M2 receptor subtype, sub maxillary gland the source of M3 receptor subtype and striatum the source of M4 receptor subtype. With the exception of cardiac tissue, no significant differences were noticeable in the affinity of dopaminergic or muscarinic cholinergic compounds tested using membrane particles or 8 microns thick slide-mounted section. In the heart, frozen sections gave lower dissociation constant and inhibition constant values than membranes. The above findings suggest that radioligand binding assay on slide-mounted tissue sections may represent a suitable technique for assessing the receptor profile of drugs under development for the treatment of disorders characterised by dopaminergic or muscarnic cholinergic dysfunction.
Tayebati
S K
SK
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Giannella
M
M
Piergentili
A
A
Pigini
M
M
Quaglia
W
W
Sabbatini
M
M
Amenta
F
F
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D005629:Frozen Sections; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000145:classification / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000145:classification / Q000378:metabolism*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism*
D018492:Dopamine Antagonists; D008024:Ligands; D018727:Muscarinic Antagonists; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic