Alpha-conotoxin ImI inhibits the alpha-bungarotoxin-resistant nicotinic response in bovine adrenal chromaffin cells.
The activity of alpha-conotoxin (alpha-CTX) ImI, from the vermivorous marine snail Conus imperialis, has been studied on mammalian nicotinic receptors on bovine chromaffin cells and at the rat neuromuscular junction. Synthetic alpha-CTX ImI was a potent inhibitor of the neuronal nicotinic response in bovine adrenal chromaffin cells (IC50 = 2.5 microM, log IC50 = 0.4 +/- 0.07), showing competitive inhibition of nicotine-evoked catecholamine secretion. Alpha-CTX ImI also inhibited nicotine-evoked 45Ca2+ uptake but not 45Ca2+ uptake stimulated by 56 mM K+. In contrast, alpha-CTX ImI had no effect at the neuromuscular junction over the concentration range 1-20 microM. Bovine chromaffin cells are known to contain the alpha3beta4, alpha7, and (possibly) alpha3beta4alpha5 subtypes. However, the secretory response of bovine chromaffin cells is not inhibited by alpha-bungarotoxin, indicating that alpha7 nicotinic receptors are not involved. We propose that alpha-CTX Iml interacts selectively with the functional (alpha3beta4 or alpha3beta4alpha5) nicotinic acetylcholine receptor to inhibit the neuronal-type nicotinic response in bovine chromaffin cells.
Broxton
N M
NM
Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia.
Down
J G
JG
Gehrmann
J
J
Alewood
P F
PF
Satchell
D G
DG
Livett
B G
BG
D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D020916:Conotoxins; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D008297:Male; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000235:genetics / Q000494:pharmacology; D009046:Motor Neurons / Q000737:chemistry / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology; D009842:Oligopeptides / Q000235:genetics / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011915:Rats, Inbred BUF; D011978:Receptors, Nicotinic / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; D002132:Calcium Radioisotopes; D002395:Catecholamines; C579165:Chrna7 protein, rat; D020916:Conotoxins; D008978:Mollusk Venoms; D009842:Oligopeptides; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C087686:alpha-conotoxin ImI; D009525:Niacin; D011189:Potassium Chloride; D000109:Acetylcholine