K+ channels and guinea-pig trachea: a possible functional modulation by GABAB receptors.
K+ channel activators represent a novel class of smooth muscle relaxant agents. There is now much evidence demonstrating that K+ channels, localized to prejunctional neurons and post-junctional smooth muscle membranes, can regulate airway smooth muscle activity, inducing smooth muscle cell membrane hyperpolarization. K+ channel activity may be influenced by some neurotransmitters, such as adenosine, serotonin and noradrenaline. More recently, it has been observed that the stimulation of GABAB receptors influences K+ channels in the hippocampus, dorsal rafe and spinal cord neurons. The aim of this study was to investigate the effects of levcromakalim in guinea-pig trachea at pre- and post-junctional sites and to evaluate whether GABAB receptors may modulate K+ channel activation. Levcromakalim (from 1 nM to 1 microM) relaxed guinea-pig trachea (IC50 10 +/- 0.9 nM) previously contracted by KCl (30 mM). This effect was reversed by a pretreatment with tetraethylammonium (10 mM) (IC50 120 +/- 0.7 nM). A 30-min pretreatment with baclofen (1 microM) or phaclofen (1 microM) failed to modify the effects of levcromakalim (IC50 18 +/- 1.0 nM and 14 +/- 0.6 nM, respectively). The contractile responses to electrical field stimulation (71.20 +/- 5.12% of acetylcholine--100 microM--contraction) was significantly (P < 0.05) reduced by a pretreatment with levcromakalim (10 nM) (54.00 +/- 6.68%). This reduction was antagonized by tetraethylammonium (10 nM) (72.20 +/- 14.27%).(ABSTRACT TRUNCATED AT 250 WORDS)
Matera
M G
MG
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, II, University of Naples, Italy.
D'Agostino
B
B
Costantino
M
M
Mangrella
M
M
Calderaro
V
V
Rossi
F
F
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D019806:Cromakalim; D004558:Electric Stimulation; D006168:Guinea Pigs; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000502:physiology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure
D001578:Benzopyrans; D001993:Bronchodilator Agents; D015221:Potassium Channels; D011758:Pyrroles; D018080:Receptors, GABA-B; D019806:Cromakalim