Differential effects of omega-conotoxin GVIA on cholinergic and non-cholinergic secretomotor neurones in the guinea-pig small intestine.
1. Ussing chambers were used to study the effects of the specific N-type Ca2+ channel antagonist, omega-conotoxin GVIA, on neurally evoked secretion across isolated submucosa/mucosa preparations from the small intestine of the guinea-pig. 2. Cholinergic and non-cholinergic neurones were stimulated with 10 microM dimethylphenylpiperazinium (DMPP). Non-cholinergic secretomotor neurones were preferentially stimulated with 100 nM 5-hydroxytryptamine (5-HT), while cholinergic secretomotor neurones were preferentially stimulated with 3 microM 5-HT in the presence of the 5-HT2 receptor antagonist ketanserin (30 nM). 3. omega-Conotoxin GVIA (1 nM-1 microM) depressed the secretion evoked by DMPP in a concentration-dependent manner, but a substantial residual response was observed. Hyoscine (100 nM) significantly depressed secretion evoked by DMPP, but did not prevent further depression of secretion by omega-conotoxin GVIA. 4. The toxin was substantially more effective when the non-cholinergic secretomotor neurones were preferentially activated with 100 nM 5-HT, with a decrease in the response of more than 75% of the control value in the presence of 1 microM omega-conotoxin GVIA. 5. omega-Conotoxin GVIA (1 microM) was relatively ineffective against secretion evoked by preferential activation of cholinergic secretomotor nuerones with 3 microM 5-HT in the presence of 30 nM ketanserin, inhibiting the response by less than 33%. However, this inhibition was significant. Both 100 nM hyoscine and 300 nM tetrodotoxin abolished this effect of omega-conotoxin GVIA. 6. It is concluded that N-type Ca2+ channels play a major role in transmitter release from non-cholinergic secretomotor neurones, but are not important for release from cholinergic secretomotor neurones in the guinea-pig small intestine.
Vremec
M A
MA
Department of Physiology, University of Melbourne, Parkville, Australia.
Bornstein
J C
JC
Wright
C E
CE
Humphrey
A
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D020866:omega-Conotoxin GVIA