Isao Yamawaki

Effects of platelet-activating factor on bioelectric properties of cultured tracheal and bronchial epithelia

To elucidate the effect of platelet-activating factor (PAF) on ion transport function of airway epithelial cells, we studied bioelectric properties of cultured tracheal and bronchial epithelia from dogs under short-circuit conditions in vitro. Addition of PAF (10(-5) mol/L) to mucosal solution of Ussing chamber increased short-circuit current of tracheal epithelium from 3.3 +/- 0.7 to 8.5 +/- 1.2 microA/cm2 (p less than 0.001). This effect was dose dependent, and there was a corresponding increase in transepithelial potential difference. In contrast, PAF was without effect when it was added to the submucosal side. Electrical properties of bronchial epithelium remained unchanged by PAF. The PAF-induced increase in short-circuit current was not affected by amiloride but abolished by diphenylamine-2-carboxylate, bumetanide, or Cl-free medium. The effects of PAF were not altered by AA-861 or U-60257, but attenuated by indomethacin and piroxicam, and dose-dependently blocked by CV 6209 and WEB 2086. Mucosal, but not submucosal, addition of PAF increased the rate of prostaglandin release from tracheal epithelium. These results suggest that PAF selectively stimulates Cl secretion across tracheal epithelium, probably through activation of its specific receptors and the subsequent production of prostaglandins.

Role of K+ channel opening and Na(+)-K+ ATPase activity in airway relaxation induced by salbutamol.

To determine the role of K+ channel opening and Na(+)-K+ ATPase activity in the beta-adrenoceptor-mediated relaxation of airway smooth muscle, we studied canine bronchial segments under isometric conditions in vitro. Relaxant responses to salbutamol were not altered by glibenclamide or apamin but inhibited by charybdotoxin, where significant inhibition was observed only at salbutamol concentrations of less than 10(-6) M. In contrast, only the relaxations induced by salbutamol at 3 x 10(-6) M and greater were sensitive to ouabain. Relaxations produced by low and high concentrations of salbutamol were selectively attenuated by charybdotoxin and ouabain, respectively, in a concentration-dependent manner. These results suggest that both Ca(2+)-activated K+ channel and Na(+)-K+ ATPase may be operative in the airway relaxation induced by low and high concentrations of the beta-adrenergic agonist, respectively.

Non‐opioid‐dependent Inhibitory Action of Loperamide on Cholinergic Neurotransmission in Canine Isolated Bronchial Smooth Muscle

Abstract— The effect of loperamide on cholinergic neurotransmission in canine bronchial smooth muscle was studied under isometric conditions in‐vitro. Addition of loperamide decreased contractile responses to electrical field stimulation in a dose‐dependent fashion, the maximal decrease from the control response and the IC50 value being 65·4 ± 5·9% and 1·5 μm, respectively. In contrast, loperamide was without effect on the responses to exogenously administered acetylcholine. The inhibitory effect of loperamide was not altered by pre‐incubation of tissues with propranol, 6‐hydroxydopamine, bicuculline, or naloxone. These results suggest that loperamide attenuates the neurally mediated airway contraction probably by inhibiting acetylcholine release from cholinergic nerve terminals through a non‐opioid‐dependent mechanism.

Guanosine-3′, 5′-cyclic monophosphate (Cyclic GMP) Stimulates Ciliary Motility in Rabbit Cultured Tracheal Epithelium

To cletenmine the effect of guanosine-3,5-cyclic monophosphate <cGMP) on aitway epithelial function, measured ciliary beat frequency (CBF) of cuitured rabbit tracheal epithetium m response to dibutyryl cGrVn?. Addition of dibutyryl cGMP increased CBF in a close-dependent fashion, an effect that was nct accompanied by alteration in intracellular denosine-3, 5-cyclic monophosphate (cmo) levels, lhese findings suggest that cGMP, one of the important second messengers, may directly stimulate respiratory ciliary motility, and thus regulate mucociliary tran

Alveolar Attachments in Emphysema of Human Lungs

port function in the airway.