We conclude that prejunctional kappa- and mu-opioid receptors attenuate the contractile response of isolated bovine trachealis muscle to EFS by inhibiting cholinergic neurotransmission. This effect is uniform throughout the trachealis muscle. delta-Opioid receptors are apparently not present in the bovine trachealis muscle. Caution must be used in extrapolating these results to the intact human. In this study little or no inhibitory effect of the opioids was observed at concentrations expected at airway receptor sites when administered by conventional techniques. However, the effect may be large enough to protect against bronchoconstriction when nebulized opioids are administered by inhalation.

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...

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The behavior of maximum expiratory flow-volume curves and partial expiratory flow-volume curves with and without volume history of total lung capacity was studied in 11 healthy subjects before and after methacholine inhalation challenge. Flow-volume curves were superimposed at absolute lung volumes by measuring thoracic gas volumes at which inspiratory maneuvers began. The results show that maximum inspiratory effort reduced significantly residual volume, either before or after challenge, while flow rates at 40% of control total lung capacity achieved with partial expiratory flow-volume curves with history of total lung capacity were significantly greater than those without history of maximal inflation. These findings are explained by the stress relaxation as an effect of volume history of total lung capacity and by the appearance of time dependence as an index of inhomogeneity of lung emptying. After methacholine the effects of volume history on maximum flows and residual volume were increased. In conclusion, the results of this study emphasize the probability of errors when only maximum expiratory flow-volume curves are used in assessment of bronchial responses