Effect of cromakalim on bronchoconstriction evoked by cholinergic nerve stimulation in guinea‐pig isolated trachea

McCaig, Dorothy; Jonckheere, B De

doi:10.1111/j.1476-5381.1989.tb12641.x

Cited by 43 publications

(22 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings show good agreement with previous studies where BRL 38227 was tested in the electrically stimulated, guinea-pig isolated trachea (Cooper et al, 1991) and cromakalim was tested against cholinergic nerveand ACh-induced bronchoconstriction in the anaesthetized guinea-pig (Ichinose & Barnes, 1990;Lewis & Raeburn, 1990). However, the present study contrasts with the work of McCaig & de Jonckheere (1989), who reported that cromakalim failed to affect responses to EFS in the guinea-pig trachea, although responses to selective, preganglionic, stimulation of vagal nerves were inhibited.…”

Section: Discussioncontrasting

confidence: 56%

See 1 more Smart Citation

Effects of BRL 38227 on neurally‐mediated responses in the guinea‐pig isolated bronchus

Good

Clapham

Hamilton

1992

British J Pharmacology

View full text Add to dashboard Cite

1 In guinea-pig isolated bronchus treated with indomethacin (2.8 gM), electrical field stimulation (EFS; 10 Hz, 0.5 ms, 60-70 V, for 10 s) evoked a tetrodotoxin (3 JM)-sensitive, biphasic contraction comprising a rapid, atropine (1 tLM)-sensitive cholinergic response succeeded by a slowly developing, capsaicin (10lM)-sensitive, non-adrenergic, non-cholinergic excitatory (NANCe) response.2 BRL 38227 (0.3-3 AM), salmeterol (0.003-3 pM) and ketotifen (1.0-300 AM) each produced concentration-dependent inhibition of both NANCe and cholinergic responses to EFS in guinea-pig isolated bronchus. 3 Substance P (SP; 1 ,M) and neurokinin A (NKA; 0.07 Mm) produced contractions equivalent in magnitude to the NANCe response to EFS, which were inhibited by salmeterol (1 pM), but not by BRL 38227 (3 Mm) or ketotifen (100 AM). 4 Acetylcholine (ACh; 6 AM) was equi-effective with the electrical activation of cholinergic neurones. BRL 38227 (3 AM) slightly inhibited responses to ACh (6 pM). Salmeterol (1 pM) and ketotifen (100 MM) markedly inhibited responses to ACh (6 Mm). 5 In bronchial rings pre-contracted with ACh (100 pM), BRL 38227 (0.1-30 pM), salmeterol (0.001-3tMM) and ketotifen (0.1-100 MM) each produced concentration-dependent relaxation. Unlike ketotifen, BRL 38227 and salmeterol only partially (18.8 ± 2.1% and 51.8 ± 3.9% respectively) reversed the ACh-induced contraction. 6 The (+ )-analogue of BRL 38227, BRL 38226 (0.3-100 MM), was without effect on responses to EFS and had no effect on the inhibition caused by BRL 38227. The K+-channel

show abstract

Section: Discussioncontrasting

confidence: 56%

“…More recently, work in guinea-pig airways has suggested that cromakalim might also exert an inhibitory effect on the activity of cholinergic and NANCe nerves (Hall & Maclagan, 1988;McCaig & de Jonckheere, 1989;Ichinose & ' Author for correspondence. Lewis & Raeburn, 1990;Burka et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Effects of BRL 38227 on neurally‐mediated responses in the guinea‐pig isolated bronchus

Good

Clapham

Hamilton

1992

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…MCCAIG and DE JONCKHEERE [3] reported that cromakalim attenuated contractions induced by peripheral vagus nerve stimulation in the isolated guinea-pig trachea, but it had no effect on contractions induced by EFS or exogenous ACh, suggesting a ganglionic effect [3]. By contrast, BURKA et al [4] and GOOD et al [5] found in isolated guinea-pig trachea that cromakalim [4] or lemakalim [5] inhibited EFSinduced contractions more than ACh-induced contractions, suggesting pre-and postjunctional effects.…”

Section: Effect On Efs-and Ach-induced Contractionsmentioning

confidence: 94%

“…Eur Respir J., 1996Respir J., , 9, 2057Respir J., -2063 In smooth muscle, potassium channel openers (KCOs) increase K + efflux across the cell membrane, resulting in cell membrane hyperpolarization, reduction of Ca 2+ influx through L-type voltage-dependent Ca 2+ -channels [1, 2], and relaxation. There is disagreement about whether the effects of KCOs occur directly at the muscle cell (postjunctional) or at the muscle cell and nerve level (pre-and postjunctional) [3][4][5][6]. For instance, in guinea-pig trachealis the adenosine triphosphate (ATP)-sensitive K + -channel (KATP) opener, cromakalim, affects the excitatory nonadrenergic noncholinergic (eNANC) nervous system [4].…”

mentioning

confidence: 99%

Postjunctional effect of pinacidil on contractility of isolated bovine trachealis

Song¹,

Rocchi²,

Lazzarotti³

et al. 1996

Eur Respir J

View full text Add to dashboard Cite

P Po os st tj ju un nc ct ti io on na al l e ef ff fe ec ct t o of f p pi in na ac ci id di il l o on n c co on nt tr ra ac ct ti il li it ty y o of f i is so ol la at te ed d b bo ov vi in ne e t tr ra ac ch he ea al li is s P. Song, D. Rocchi, M. Lazzarotti, E. Crimi, K. Rehder, V. BrusascoPostjunctional effect of pinacidil on contractility of isolated bovine trachealis. P. Song, D. Rocchi, M. Lazzarotti, E. Crimi, K. Rehder, V. Brusasco. ERS Journals Ltd 1996. ABSTRACT: Potassium channel openers hyperpolarize the smooth muscle cell membrane and relax airway smooth muscle. In this study, pre-and postjunctional effects of pinacidil ((±) N-cyano-N'-(4-pyridil)-N"-(1,2,2-trimethylpropyl)-guanidine monohydrated), an adenosine triphosphate (ATP)-sensitive K + -channel opener, were determined in isolated bovine trachealis. The effects of pinacidil on the frequency-response to electrical field stimulation (EFS), 0.1-32 Hz, and on the concentration-response to acetylcholine (ACh), 10 -9 -10 -4 M, were compared in muscle strips from six animals. In addition, the effect of pinacidil on the inhibitory nonadrenergic noncholinergic (iNANC) system was evaluated in histamine-contracted muscle strips from another eight animals.Pinacidil (10 -6 or 10 -5 M) shifted both the EFS frequency-response and the ACh concentration-response curves significantly (p<0.01) to the right. Glibenclamide (10 -7 -10 -5 M) antagonized these responses in a concentration-dependent manner. The inhibitory effects of pinacidil on contractions of the same magnitude induced by EFS or exogenous ACh were not significantly different (p=0.11), suggesting that pinacidil had only a postjunctional effect. Pinacidil had no effect on iNANC-mediated muscle relaxation.We conclude that pinacidil attenuates the contraction of isolated bovine tracheal smooth muscle by postjunctional mechanisms. Eur Respir J., 1996Respir J., , 9, 2057Respir J., -2063 In smooth muscle, potassium channel openers (KCOs) increase K + efflux across the cell membrane, resulting in cell membrane hyperpolarization, reduction of Ca 2+ influx through L-type voltage-dependent Ca 2+ -channels [1, 2], and relaxation. There is disagreement about whether the effects of KCOs occur directly at the muscle cell (postjunctional) or at the muscle cell and nerve level (pre-and postjunctional) [3][4][5][6]. For instance, in guinea-pig trachealis the adenosine triphosphate (ATP)-sensitive K + -channel (KATP) opener, cromakalim, affects the excitatory nonadrenergic noncholinergic (eNANC) nervous system [4]. If the effect of the KCOs is predominantly on the eNANC nervous system, it may not be demonstrable in airway tissue from animals with no eNANC nerves, such as the human and bovine airways. In these species, the effect of KCOs would occur only through inhibition of excitatory cholinergic nerves, stimulation of inhibitory nonadrenergic noncholinergic (iNANC) nerves, or a direct effect on the muscle. Importantly, a direct effect on the muscle may be easier to demonstrate in airways from species without eN...

show abstract

“…Taylor et al (3) re ported that cromakalim is an effective inhibitor of spon taneous tone in isolated human bronchioles. Recently, cromakalim was reported to modulate neurotransmis sion in the guinea pig trachea (4,5), and its possible use in the treatment of asthma is now under investiga tion.…”

mentioning

confidence: 99%

Effects of Anti-Asthma Drugs and Potassium Channel Openers on Neurally-Mediated Contraction of Isolated Guinea Pig Trachea

Yamamoto

Shikada

Tanaka

1992

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-Keywords: Anti-asthma drugs, Neurally-mediated contraction, Trachea (guinea pig)The airways are under the control of the autonomic nervous system. Abnormalities in autonomic regulation of the airway, such as an increase in cholinergic activ ity, may underlie bronchial hyperreactivity and contrib ute to the bronchoconstriction of asthma (1). 8-Adreno ceptor agonist and methylxanthines have been widely used to treat asthma, because of their airway smooth muscle relaxant activity. Glucocorticoid therapy has been also applied in the treatment of asthma, based on its anti-inflammatory activity. However, actual involve ment of these mechanisms in the treatment of asthma does not seem to be clear.The potassium channel openers posses not only vasorelaxing activity but also bronchodilation activity in isolated guinea pig trachea (2). Taylor et al. (3) re ported that cromakalim is an effective inhibitor of spon taneous tone in isolated human bronchioles. Recently, cromakalim was reported to modulate neurotransmis sion in the guinea pig trachea (4, 5), and its possible use in the treatment of asthma is now under investiga tion.In this study, we investigated the effects of iso proterenol, aminophylline, hydrocortisone and potas sium channel openers on the increase in intraluminal pressure (ILP) of isolated guinea pig trachea. The ILP was evoked by: 1) stimulation of the vagus nerve, 2) transmural field stimulation and 3) exogenously applied acetylcholine (ACh), and we compared the modes of action of these drugs. The methods of Blackman and McCaig (6) were modified and used. Briefly, male Hartley guinea pigs (250-400 g) were killed by a blow to the head, and the trachea was excised with the right vagus nerve. The preparation was cannulated at each end, set up horizon tally and maintained at 37°C in an 80-ml organ bath containing aerated modified Tyrode solution. The lu men of the trachea was filled with the Tyrode solution. The composition of the Tyrode solution was as follows: 137 mM NaCl, 2.7 mM KC1, 1.8 mM CaC12, LO MM MgC12, 20 mM NaHCO3, 0.32 mM NaH2PO4 and 11 mM dextrose. One end of the trachea was closed and the other end was attached to a pressure transducer (TP-400T, Nihon Kohden) to record ILP.The trachea was equilibrated for 50 min and the re sponse to 100 p.t M histamine was recorded and washed. Histamine increased ILP to 42 ± 2 mmHg (n = 7), and the responses of the following experiments were ex pressed as percentages of the histamine response. Fifty minutes after the washout of histamine, responses to vagus nerve and transmural field stimulation were obtained. The vagus nerve and transmural field stimula tion were delivered by an electronic stimulator (SEN

show abstract

Effect of cromakalim on bronchoconstriction evoked by cholinergic nerve stimulation in guinea‐pig isolated trachea

Cited by 43 publications

References 14 publications

Effects of BRL 38227 on neurally‐mediated responses in the guinea‐pig isolated bronchus

Effects of BRL 38227 on neurally‐mediated responses in the guinea‐pig isolated bronchus

Postjunctional effect of pinacidil on contractility of isolated bovine trachealis

Effects of Anti-Asthma Drugs and Potassium Channel Openers on Neurally-Mediated Contraction of Isolated Guinea Pig Trachea

Contact Info

Product

Resources

About