Involvement of both L- and N-type voltage-dependent Ca2+ channels in KCl- and veratridine-evoked transmitter release from non-adrenergic, non-cholinergic nerves in the rabbit iris sphincter muscle.
To determine which types of voltage-dependent Ca2+ channels mediate tachykinin release in the isolated rabbit iris sphincter muscle, we examined the effects of several Ca2+ channel modulators on contractions induced by either an elevation of the extracellular KCl concentration or application of the Na+ channel activator veratridine. Contractions caused by either 45.9 mM KCl or veratridine (10 microM) were inhibited by spantide (10 microM), a tachykinin receptor antagonist, and capsaicin (10 microM), a tachykinin-depleting agent, but were not changed by atropine. Nicardipine, an L-type Ca2+ channel blocker, inhibited contractions induced by KCl and veratridine in a concentration-dependent manner. omega-Conotoxin GVIA (1 microM), an N-type Ca2+ channel blocker, inhibited only contractions induced by lower concentrations of KCl, both when applied alone and when combined with nicardipine. Bay K 8644, an L-type Ca2+ channel activator, caused a spantide- and nicardipine-sensitive contraction in muscles partially depolarized with 15.9 mM KCl, and enhanced contractions induced by 15.9 mM KCl and veratridine (2 microM). omega-Agatoxin IVA (0.3 microM), a P-type voltage-dependent Ca2+ channel blocker, did not affect contractions induced by either KCl or veratridine. Contractions induced by exogenous substance P were not modified by any of the Ca2+ channel blockers or by Bay K 8644. These results suggest that, in the rabbit iris sphincter muscle. L- and N-type voltage-dependent Ca2+ channels are involved in neurotransmitter release from tachykininergic nerves elicited by high KCl and by veratridine.
Kageyama
M
M
Ophthalmic Research Division, Santen Pharmaceutical Co., Ltd., Ikoma-shi, Japan.
Fujita
H
H
Nakata
K
K
Shirasawa
E
E
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D007498:Iris / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D011817:Rabbits; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D015222:Sodium Channels / Q000187:drug effects; D013111:Spider Venoms / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014701:Veratridine / Q000494:pharmacology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D000700:Analgesics; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018727:Muscarinic Antagonists; D010455:Peptides; D018039:Receptors, Tachykinin; D015222:Sodium Channels; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D013373:Substance P; D011189:Potassium Chloride; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001285:Atropine; C042867:spantide; D020866:omega-Conotoxin GVIA; D009529:Nicardipine; D002211:Capsaicin