[beta-adrenoceptor subtypes involved in relaxations of guinea-pig gastrointestinal smooth muscles: distribution and signaling pathway of beta 3-adrenoceptors].
The distribution and signaling pathway of beta 3-adrenoceptors involved in relaxations were examined in guinea-pig gastrointestinal smooth muscles. In esophagus, beta 1-adrenoceptors participate in isoprenaline-induced relaxations. However, both beta 2- and beta 3-adrenoceptors contribute to the relaxations in taenia caecum. In gastric fundus, duodenum, and ileum, beta 3-adrenoceptors were responsible for the relaxant responses. These results suggest that functional beta 3-adrenoceptors are present in four smooth muscles except esophagus. This was strongly supported by molecular analyses with RT-PCR, showing the expression of beta 3-adrenoceptor mRNA in the four tissues. beta 3-Adrenoceptor-mediated relaxations were unaffected by both an adenylyl cyclase inhibitor, SQ-22,536 (100 microM), and a PKA inhibitor, H-89 (10 microM), in guinea-pig gastric fundus smooth muscle. Furthermore, in the presence of SQ-22,536 (100 microM), the stimulation of beta 3-adrenoceptors elicited relaxations without an elevation of cAMP, indicating the involvement of cAMP-independent mechanism(s). beta 3-Adrenoceptor-mediated, cAMP-independent relaxations were significantly diminished by a Kv channel blocker, 4-aminopyridine (3 mM). These results indicate that beta 3-adrenoceptors play a primary role in relaxations of guinea-pig gastrointestinal smooth muscles and 4-aminopyridine-sensitive Kv channels participate in cAMP-independent smooth muscle relaxations in response to the activation of beta 3-adrenoceptors.
Horinouchi
Takahiro
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Tanaka
Yoshio
Y
Koike
Katsuo
K
D000818:Animals; D004068:Digestive System Physiological Phenomena; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D022702:Receptors, Adrenergic, beta-3