Effect of potassium channel blockers on relaxations to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea.
Nonadrenergic, noncholinergic (NANC) relaxations were elicited by field stimulation (1-16 Hz, 1 msec, 12 V for 15 sec) of guinea pig trachea desensitized with capsaicin (3 microM); pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. The nitric oxide (NO) synthase inhibitor L-nitro-N-arginine (L-NNA) significantly inhibited these responses, which is indicative of NO involvement. The ability of the large conductance Ca(++)-activated K+ channel antagonists iberiotoxin (IbTx) and charybdotoxin (ChTx) and the small conductance Ca(++)-activated K+ channel antagonist apamin to modify relaxations to NANC nerve stimulation and to the NO donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) was studied. Both IbTx (100 nM) and ChTx (100 nM) were found to inhibit the L-NNA-sensitive relaxations elicited by field stimulation and to inhibit the relaxations to SIN-1. In contrast, apamin did not inhibit the relaxations to either field stimulation or SIN-1. These results suggest that in the guinea pig trachea, responses to endogenous or exogenously added NO are at least in part mediated by the large conductance Ca(++)-activated K+ channel.
Ellis
J L
JL
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland.
Conanan
N D
ND
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D018999:Charybdotoxin; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D012604:Scorpion Venoms / Q000494:pharmacology; D014132:Trachea / Q000502:physiology*
D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; C064719:iberiotoxin; D001120:Arginine; D008981:Molsidomine