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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/L923    most recent 00185.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Osawa, Y. Articles by Emala, C. W. Search for Related Content PubMed PubMed Citation Articles by Osawa, Y. Articles by Emala, C. W.

Functional expression of the GABA_B receptor in human airway smooth muscle

Departments of ¹Anesthesiology, ²Surgery, and ³Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, and ⁴Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Submitted 22 May 2006 ; accepted in final form 6 July 2006

-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABA_A/GABA_C) and metabotropic (GABA_B) receptors (R). In addition to their location on neurons, GABA and functional GABA_B receptors have been detected in nonneuronal cells in peripheral tissue. Although the GABA_BR has been shown to function as a prejunctional inhibitory receptor on parasympathetic nerves in the lung, the expression and functional coupling of GABA_B receptors to G_i in airway smooth muscle itself have never been described. We detected the mRNA encoding multiple-splice variants of the GABA_BR1 and GABA_BR2 in total RNA isolated from native human and guinea pig airway smooth muscle and from RNA isolated from cultured human airway smooth muscle (HASM) cells. Immunoblots identified the GABA_BR1 and GABA_BR2 proteins in human native and cultured airway smooth muscle. The GABA_BR1 protein was immunohistochemically localized to airway smooth muscle in guinea pig tracheal rings. Baclofen, a GABA_BR agonist, elicited a concentration-dependent stimulation of [³⁵S]GTPS binding in HASM homogenates that was abrogated by the GABA_BR antagonist CGP-35348. Baclofen also inhibited adenylyl cyclase activity and induced ERK phosphorylation in HASM. Another GABA_BR agonist, SKF-97541, mimicked while pertussis toxin blocked baclofen’s effect on ERK phosphorylation, implicating G_i protein coupling. Functional GABA_B receptors are expressed in HASM. GABA may modulate an uncharacterized signaling cascade via GABA_B receptors coupled to the G_i protein in airway smooth muscle.

G protein; adenylyl cyclase; mitogen-activated protein kinase; [³⁵S]GTPS binding; guinea pig; trachea

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