K-PIG TRACHEA - A POSSIBLE FUNCTIONAL MODULATION BY GABA(B) RECEPTORS( CHANNELS AND GUINEA)

K+ channel activators represent a novel class of smooth muscle relaxan t agents. There is now much evidence demonstrating that K+ channels, l ocalized to prejunctional neurones and post-junctional smooth muscle m embranes, can regulate airway smooth muscle activity, inducing smooth muscle cell membrane hyperpolarization. K+ channel activity may be inf luenced by some neurotransmitters, such as adenosine, serotonin and no radrenaline. More recently, it has been observed that the stimulation of GABA(B) receptors influences K+ channels in the hippocampus, dorsal rafe and spinal cord neurons. The aim of this study was to investigat e the effects of levcromakalim in guinea-pig trachea at pre- and post- junctional sites and to evaluate whether GABA(B) receptors may modulat e K+ channel activation. Levcromakalim (from 1 nM to 1 mu M) relaxed g uinea-pig trachea (IC50 10+/-0.9 nM) previously contracted by KCl (30 mM). This effect was reversed by a pretreatment with tetraethylammoniu m (10 mM) (IC50 120+/-0.7 nM). A 30-min pretreatment with baclofen (1 mu M) or phaclofen (1 mu M) failed to modify the effects of levcromaka lim (IC50 18+/-1.0 nM and 14+/-0.6 nM, respectively). The contractile responses to electrical field stimulation (71.20+/-5.12% of acetylchol ine-100 mu M-contraction) was significantly (P<0.05) reduced by a pret reatment with levcromakalim (10 nM) (54.00+/-6.68%). This reduction wa s antagonized by tetraethylammonium (10 nM) (72.20+/-14.27%). A 30-min pretreatment with baclofen (1 mu M) significantly (P<0.05) enhanced t he effect of levcromakalim on electrical field stimulation, whereas ph aclofen (1 mu M) significantly (P<0.05) antagonized these responses. T hese data demonstrate that K+ channels may be localized both to prejun ctional and post-junctional post-ganglionic sites, and may play an imp ortant role in modulating airway responsiveness. In fact, they may act at the prejunctional neurones, inhibiting the release of contractile neurotransmitter, or at the post-junctional sites, hyperpolarizing smo oth muscle airway membranes. Moreover, the present study seems to demo nstrate that K+ channels localized on the prejunctional post-ganglioni c nerves may be influenced by GABA(B) receptors.