Involvement of K+ channels in the relaxant effect of vasoactive intestinal peptide and atrial natriuretic peptide in isolated guinea-pig trachea.
The possible contribution of K+ channel activation to airway smooth muscle relaxation induced by vasoactive intestinal peptide (VIP) and atrial natriuretic peptide (ANP) was investigated in isolated guinea-pig trachea. Concentration-relaxation (CR) curves were assessed in preparations precontracted by 30 mM K+, 124 mM K+ or histamine either alone or in the presence of a K+ channel blocker: iberiotoxin (IbTX), glipizide, tetraethylammonium (TEA) or Ba2+. VIP completely relaxed contractions induced by histamine but had a lower effectiveness against those induced by 30 mM K+ and 124 mM K+. IbTX and TEA shifted the CR curve for VIP 5 and 14 times to the right, respectively. Glipizide and Ba2+ did not significantly antagonize the action of VIP. ANP relaxed contractions induced by histamine and 30 mM K+ but failed to relax those elicited by 124 mM K+. IbTX and TEA shifted the CR curve for ANP 8 and 46 times to the right, respectively. Glipizide and Ba2+ suppressed the maximal effect produced by ANP, and glipizide also shifted the CR curve to the left. The K+ channel opener levcromakalim relaxed tracheal contractions induced by histamine and 30 mM K+ but not those induced by 124 mM K+. Glipizide caused a 5-fold rightward shift of the CR curve for levcromakalim whereas IbTX shifted the curve to the left and increased the maximal relaxant effect. The Ca2+ channel blocker isradipine completely relaxed contractions induced by 30 mM K+ and 124 mM K+ but only partially relaxed those contracted by histamine. All four K+ channel blockers increased the maximal relaxant effect and shifted the CR curve for isradipine to the left. The results suggest that airway smooth muscle relaxation produced by VIP and ANP involves activation of large-conductance Ca(2+)-activated K+ channels (BKCa) and further that ANP may possibly activate other types of K+ channels additional to BKCa.
Thirstrup
S
S
Institute of Pharmacology, University of Aarhus, Denmark. ST@farm.aau.dk
Nielsen-Kudsk
J E
JE
Mellemkjaer
S
S
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019806:Cromakalim; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017275:Isradipine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D014660:Vasoactive Intestinal Peptide; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D017275:Isradipine