Involvement of K+ channels in the relaxant effect of vasoactive intestinal peptide and atrial natriuretic peptide in isolated guinea-pig trachea

被引:10
作者
Thirstrup, S [1 ]
NielsenKudsk, JE [1 ]
Mellemkjaer, S [1 ]
机构
[1] UNIV COPENHAGEN, RIGSHOSP, DEPT MED B, DK-2100 COPENHAGEN, DENMARK
关键词
ANP (atrial natriuretic polypeptide); VIP (vasoactive intestinal polypeptide); K+ channel; levcromakalim; Ca2+ channel blocker; isradipine; trachea; smooth muscle; airway;
D O I
10.1016/S0014-2999(96)00855-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Ca2+-activated K+ channels (BKCa) and further that ANP may possibly activate other types of K+ channels additional to BKCa.
引用
收藏
页码:253 / 259
页数:7
相关论文
共 31 条
[1]  
AIZAWA H, 1994, LUNG, V172, P159
[2]   ELECTRICAL AND MECHANICAL EFFECTS OF BRL34915 IN GUINEA-PIG ISOLATED TRACHEALIS [J].
ALLEN, SL ;
BOYLE, JP ;
CORTIJO, J ;
FOSTER, RW ;
MORGAN, GP ;
SMALL, RC .
BRITISH JOURNAL OF PHARMACOLOGY, 1986, 89 (02) :395-405
[3]   EFFECT OF INHALED ATRIAL-NATRIURETIC-PEPTIDE ON METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN ASTHMA [J].
ANGUS, RM ;
MCCALLUM, MJA ;
THOMSON, NC .
CLINICAL AND EXPERIMENTAL ALLERGY, 1994, 24 (08) :784-788
[4]   INHIBITORY NANC NERVES IN HUMAN TRACHEAL SMOOTH-MUSCLE - A QUEST FOR THE NEUROTRANSMITTER [J].
BELVISI, MG ;
STRETTON, CD ;
MIURA, M ;
VERLEDEN, GM ;
TADJKARIMI, S ;
YACOUB, MH ;
BARNES, PJ .
JOURNAL OF APPLIED PHYSIOLOGY, 1992, 73 (06) :2505-2510
[5]   K-CA CHANNEL ANTAGONISTS REDUCE NO DONOR-MEDIATED RELAXATION OF VASCULAR AND TRACHEAL SMOOTH-MUSCLE [J].
BIALECKI, RA ;
STINSONFISHER, C .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1995, 268 (01) :L152-L159
[6]  
BKAILY G, 1990, PROG CLIN BIOL RES, V327, P507
[7]   EVIDENCE THAT PART OF THE NANC RELAXANT RESPONSE OF GUINEA-PIG TRACHEA TO ELECTRICAL-FIELD STIMULATION IS MEDIATED BY NITRIC-OXIDE [J].
CHUN, GL ;
RAND, MJ .
BRITISH JOURNAL OF PHARMACOLOGY, 1991, 102 (01) :91-94
[8]   VASOACTIVE INTESTINAL POLYPEPTIDE PROMOTES CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE ACCUMULATION IN GUINEA-PIG TRACHEA [J].
FRANDSEN, EK ;
KRISHNA, GA ;
SAID, SI .
BRITISH JOURNAL OF PHARMACOLOGY, 1978, 62 (03) :367-369
[9]   USE OF TOXINS TO STUDY POTASSIUM CHANNELS [J].
GARCIA, ML ;
GALVEZ, A ;
GARCIACALVO, M ;
KING, VF ;
VAZQUEZ, J ;
KACZOROWSKI, GJ .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1991, 23 (04) :615-646
[10]   RELAXATION OF ISOLATED GUINEA-PIG TRACHEA, BRONCHI AND PULMONARY-ARTERIES PRODUCED BY VASOACTIVE INTESTINAL PEPTIDE (VIP) [J].
HAND, JM ;
LARAVUSO, RB ;
WILL, JA .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1984, 98 (02) :279-284