Beta1-adrenoceptor-mediated relaxation with isoprenaline and the role of MaxiK channels in guinea-pig esophageal smooth muscle.
The possible functional coupling between beta1-adrenoceptor and MaxiK channels which results in smooth muscle relaxation was examined in the guinea-pig esophageal muscularis mucosae. Isoprenaline-elicited relaxation of esophageal smooth muscle was confirmed to be mediated through beta1-adrenoceptors as the response was competitively antagonized by a beta1-selective antagonist atenolol with a pA2 value of 7.01. Iberiotoxin (IbTx, 10(-7) M), a selective MaxiK channel inhibitor, substantially diminished the relaxant response to isoprenaline. The extent of the MaxiK channel contribution to the relaxant response was 15-40% of the control response when estimated as the E50%-Emax responses to isoprenaline. The relaxation to isoprenaline was also attenuated by high-KCl (80 mM) to the same degree as the relaxant response generated in the presence of IbTx, and thus the estimated extent of the K+ channel contribution was 10-40%. These findings indicate that beta1-adrenoceptors are substantially coupled with MaxiK channels to produce relaxation of esophageal smooth muscle in the guinea-pig. Although MaxiK channels account for the contribution of K+ channels to the beta1-adrenoceptor-mediated relaxation in this smooth muscle preparation, their contribution seems to be less when compared to the beta2-adrenoceptor-mediated relaxation of tracheal smooth muscle.
Tanaka
Yoshio
Y
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi-City, Chiba, Japan. yotanaka@phar.toho-u.ac.jp
Shinoda
Keiko
K
Sekiya
Sarasa
S
Yamaki
Fumiko
F
Shibano
Mari
M
Yamashita
Yoko
Y
Horinouchi
Takahiro
T
Koike
Katsuo
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D018342:Receptors, Adrenergic, beta-1; D011189:Potassium Chloride; C064719:iberiotoxin; D007545:Isoproterenol