Inhibition of neuromuscular transmission in the myenteric plexus of guinea-pig ileum by omega-conotoxins GVIA, MVIIA, MVIIC and SVIB.
1. The effects of a number of Ca2+ channel blockers on the transmural electrical stimulation or receptor agonist-elicited contractile responses of guinea-pig ileum were compared. 2. omega-Conotoxins (MVIIA, GVIA, SVIB and MVIIC), but not omega-agatoxin IVA, completely blocked the twitch responses evoked by low frequency (0.1 Hz) transmural stimulation without inhibition of the contractures evoked by exogenous acetylcholine. The concentration-inhibition curves were shifted by changes of external Ca2+. 3. The tetanic contractures produced by a high frequency (30 Hz) train of stimulation were inhibited by omega-conotoxins by only 25-30%, except for omega-conotoxin MVIIC, which produced about 55% inhibition, all significantly less than that produced by atropine (about 70%) or tetrodotoxin (about 85%). Combinations of omega-conotoxins did not produce additive inhibitory effects. 4. The four omega-conotoxins as well as atropine produced similar partial inhibition (53-62%) of the contractures evoked by dimethylphenylpiperazinium, while tetrodotoxin inhibited the contracture completely. 5. Nifedipine and Ni2+ depressed the nerve stimulation-evoked twitch response and tetanic contracture as well as acetylcholine contracture. 6. These observations suggest that, in the myenteric plexus, a subset of N-type Ca2+ channel dominates under low frequency stimulation, while high frequency stimulation may recruit additional channels and non-cholinergic pathways.
Hong
S J
SJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Roan
Y F
YF
Chang
C C
CC
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020916:Conotoxins; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D020916:Conotoxins; D018691:Excitatory Amino Acid Antagonists; D010456:Peptides, Cyclic; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; C055407:conotoxin GV; D009543:Nifedipine