A novel acetylcholine receptor-related peptide blocks canine cardiac ganglia and inhibits the nicotinic receptor of PC-12 cells.
A 13 amino acid peptide from the calf muscle acetylcholine receptor has been previously shown to bind both snake neurotoxins and acetylcholine. In the experiments reported here a modified complementary peptide (cAChR) derived from that acetylcholine receptor peptide was tested for biological activity in a canine heart preparation. It was expected that the modified complementary peptide would exhibit either acetylcholine-like effects or acetylcholine inhibiting effects, since, as a complementary peptide to the receptor, it should resemble acetylcholine. In these studies cAChR was administered via the sinus node artery of dog hearts in intact animals which were anesthetized with pentobarbital, intubated, and prepared with local cardiac electrograms and force gauges. cAChR was also injected directly into thoracic sympathetic ganglia. Both approaches demonstrated cAChR inhibition of neural transmission, cAChR was added to the medium of carbachol stimulated PC-12 cells. In these cells, derived from a rat pheochromocytoma, sodium flux is controlled by neural nicotinic receptors. With or without preincubation cAChR inhibited carbachol stimulation of sodium flux, exhibiting a Ki of approximately 9 x 10(-5) (similar to that of hexamethonium). Thus cAChR appears to be a novel synthetic peptide which interrupts nicotinic cholinergic neural transmission by acting as an antagonist of the neural nicotinic receptor.
Radding
W
W
Department of Pathology, University of Alabama, Birmingham 35294-6815.
Hageman
G R
GR
Gantenberg
N S
NS
Bradley
R J
RJ
Liu
Y
Y
Kemp
G
G
D000595:Amino Acid Sequence; D000818:Animals; D002217:Carbachol; D002460:Cell Line; D004285:Dogs; D004594:Electrophysiology; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008969:Molecular Sequence Data; D009431:Neural Conduction / Q000187:drug effects*; D018733:Nicotinic Antagonists; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism
D018733:Nicotinic Antagonists; D010455:Peptides; C078698:cAChR ligand; D002217:Carbachol; D012964:Sodium