Activities of 5-methylfurfuryltrimethylammonium iodide and related compounds at vascular endothelial muscarinic receptors of the rat aorta.
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 less than dl-muscarine less than 5-HMFT = 5-CMFT less than 5-MOFT less than 5-BMFT less than 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 greater than dl-muscarine greater than 5-HMFT greater than 5-CMFT. Atropine and scopolamine antagonized relaxations by furan analogs. KB values for atropine and scopolamine against ACh, 5-MFT or 5-HMFT as agonist were not different, indicating that these agonists and antagonists were acting at the same muscarinic receptors. The KB of atropine and of scopolamine increased when 5-CMFT was used as an agonist, indicating that 5-CMFT may cause relaxation by acting at other sites besides endothelial muscarinic receptors. The endothelial muscarinic receptor might be classified tentatively as of M2 or Ms type. These studies did not exclude the possible heterogeneity of the endothelial muscarinic receptors.
Horst
M A
MA
Department of Pharmacology, School of Medicine, Vanderbilt University Medical Center North, Nashville, TN 37232.
Sastry
B V
BV
Landon
E J
EJ
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009116:Muscarine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014403:Tubocurarine / Q000494:pharmacology
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; C008446:5-methylfurtrethonium; D009538:Nicotine; D009116:Muscarine; D014403:Tubocurarine