Activities of 5-methylfurfuryltrimethylammonium iodide and related compounds at vascular endothelial muscarinic receptors of the rat aorta

Abstract

5-Methylfurfuryltrimethylammonium iodide (5-MFT) is a furan analog of muscarine and was studied for its cholinergic activity at vascular endothelial receptors of the rat aorta. Other related compounds have different substitutions at position 5 of the furan ring and include the following compounds: 5-hydroxymethyl- (5-HMFT), 5-chloromethyl- (5-CMFT), 5-bromomethyl- (5-BMFT), 5-iodomethyl- (5-IMFT), and 5-methoxy- (5-MOFT) furfuryltrimethylammonium salts. The furan analogs relaxed helical strips of rat aorta which contracted with norepinephrine (10-6 M). These relaxations were endothelial cell-dependent. The ED50's for muscarinic activities increased in the following order: 5-MFT = ACh < dl-muscarine < 5-HMFT = 5-CMFT < 5-MOFT < 5-BMFT < 5-IMFT. Among the furan analogs, 5-MFT was found to be a full agonist at the endothelial cells; other furan analogs were only partial agonists. The affinities and relative intrinsic efficacies of the most potent analogs decreased in the following order: ACh = 5-MFT > dl-muscarine > 5-HMFT > 5-CMFT. Atropine and scopolamine antagonized relaxations by furan analogs. K(B) values for atropine and scopolamine against ACh, 5-MFT or 5-HMFT as agonist were not different, indicating that the agonists and antagonists were acting at the same muscarinic receptors. The K(B) of atropine and scopolamine increased when 5-CMFT was used as an agonist, indicating that 5-CFMT may cause relaxation by acting at other sites besides endothelial muscarinic receptors. The endothelial muscarinic receptor might be classified tentatively as of M2 or M(s) type. These studies did not exclude the possible heterogeneity of the endothelial muscarinic receptors.