Relaxant Effects of the Potassium Channel Activators BRL 38227 and Pinacidil on Guinea-pig and Human Airway Smooth Muscle, and Blockade of Their Effects by Glibenclamide and BRL 31660

1993 ◽  
Vol 6 (1) ◽  
pp. 77-86 ◽  
Author(s):  
D.R. Buckle ◽  
J.R.S. Arch ◽  
N.E. Bowring ◽  
K.A. Foster ◽  
J.F. Taylor ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Potassium Channel ◽  
Airway Smooth Muscle ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Potassium Channel Activators

Functional expression of the GABAB receptor in human airway smooth muscle

2006 ◽  
Vol 291 (5) ◽  
pp. L923-L931 ◽  
Author(s):  
Yoko Osawa ◽  
Dingbang Xu ◽  
David Sternberg ◽  
Joshua R. Sonett ◽  
Jeanine D’Armiento ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Gabab Receptor ◽  
Splice Variants ◽  
Functional Expression ◽  
Functional Coupling ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Erk Phosphorylation

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABAA/GABAC) and metabotropic (GABAB) receptors (R). In addition to their location on neurons, GABA and functional GABAB receptors have been detected in nonneuronal cells in peripheral tissue. Although the GABABR has been shown to function as a prejunctional inhibitory receptor on parasympathetic nerves in the lung, the expression and functional coupling of GABAB receptors to Gi in airway smooth muscle itself have never been described. We detected the mRNA encoding multiple-splice variants of the GABABR1 and GABABR2 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 GABABR1 and GABABR2 proteins in human native and cultured airway smooth muscle. The GABABR1 protein was immunohistochemically localized to airway smooth muscle in guinea pig tracheal rings. Baclofen, a GABABR agonist, elicited a concentration-dependent stimulation of [35S]GTPγS binding in HASM homogenates that was abrogated by the GABABR antagonist CGP-35348. Baclofen also inhibited adenylyl cyclase activity and induced ERK phosphorylation in HASM. Another GABABR agonist, SKF-97541, mimicked while pertussis toxin blocked baclofen’s effect on ERK phosphorylation, implicating Gi protein coupling. Functional GABAB receptors are expressed in HASM. GABA may modulate an uncharacterized signaling cascade via GABAB receptors coupled to the Gi protein in airway smooth muscle.

NK2-receptor mediated contraction in monkey, guinea-pig and human airway smooth muscle

Neuropeptides ◽  
1999 ◽  
Vol 33 (1) ◽  
pp. 27-34 ◽  
Author(s):  
C.A. Rizzo ◽  
A.F. Valentine ◽  
R.W. Egan ◽  
W. Kreutner ◽  
J.A. Hey
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Nk2 Receptor

The Action of a Potassium Channel Activator, BRL 38227 (Lemakalim), on Human Airway Smooth Muscle

1990 ◽  
Vol 142 (6_pt_1) ◽  
pp. 1384-1389 ◽  
Author(s):  
Judith L. Black ◽  
Carol L. Armour ◽  
Peter R. A. Johnson ◽  
Lorraine A. Alouan ◽  
Peter J. Barnes
Keyword(s):  
Smooth Muscle ◽  
Potassium Channel ◽  
Airway Smooth Muscle ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Potassium Channel Activator ◽  
Channel Activator

scholarly journals Expression and Function of Voltage-dependent Potassium Channel Genes in Human Airway Smooth Muscle

1996 ◽  
Vol 271 (22) ◽  
pp. 13239-13243 ◽  
Author(s):  
Sarvesh Adda ◽  
Bernd K. Fleischmann ◽  
Bruce D. Freedman ◽  
Ming-fu Yu ◽  
Douglas W. P. Hay ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Potassium Channel ◽  
Airway Smooth Muscle ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Voltage Dependent ◽  
And Function

Melatonin MT2 receptor is expressed and potentiates contraction in human airway smooth muscle

2021 ◽  
Author(s):  
Haruka Sasaki ◽  
Yi Zhang ◽  
Charles W Emala ◽  
Kentaro Mizuta
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Fiber Formation ◽  
Melatonin Receptors ◽  
Human Airway Smooth Muscle ◽  
Nocturnal Asthma ◽  
Smooth Muscle Tone ◽  
Human Airway

Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms. Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT1 receptor which couples to both Gq and Gi proteins, and the MT2 receptor which couples to Gi. We investigated whether melatonin receptors are expressed on airway smooth muscle, whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca2+]i) which modulate airway smooth muscle tone, and whether they promote airway smooth muscle cell proliferation. We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR, immunoblotting, and immunohistochemistry. Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10 - 100 µM) or the non-selective MT1/MT2 agonist ramelteon (10 µM) significantly inhibited forskolin-stimulated cAMP accumulation in HASM cells, which was reversed by the Gαi protein inhibitor pertussis toxin or knockdown of the MT2 receptor by its specific siRNA. Although melatonin by itself did not induce an initial [Ca2+]i increase and airway contraction, melatonin significantly potentiated acetylcholine-stimulated [Ca2+]i increases, stress fiber formation through the MT2 receptor in HASM cells, and attenuated the relaxant effect of isoproterenol in guinea pig trachea. These findings suggest that the melatonin MT2 receptor is expressed in ASM, and modulates airway smooth muscle tone via reduced cAMP production and increased [Ca2+]i.

scholarly journals Targeting the restricted α-subunit repertoire of airway smooth muscle GABAA receptors augments airway smooth muscle relaxation

2012 ◽  
Vol 302 (2) ◽  
pp. L248-L256 ◽  
Author(s):  
George Gallos ◽  
Peter Yim ◽  
Sucie Chang ◽  
Yi Zhang ◽  
Dingbang Xu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Human Airway Smooth Muscle ◽  
Α Subunit ◽  
Human Airway ◽  
Laser Capture

The prevalence of asthma has taken on pandemic proportions. Since this disease predisposes patients to severe acute airway constriction, novel mechanisms capable of promoting airway smooth muscle relaxation would be clinically valuable. We have recently demonstrated that activation of endogenous airway smooth muscle GABAA receptors potentiates β-adrenoceptor-mediated relaxation, and molecular analysis of airway smooth muscle reveals that the α-subunit component of these GABAA receptors is limited to the α4- and α5-subunits. We questioned whether ligands with selective affinity for these GABAA receptors could promote relaxation of airway smooth muscle. RT-PCR analysis of GABAA receptor subunits was performed on RNA isolated by laser capture microdissection from human and guinea pig airway smooth muscle. Membrane potential and chloride-mediated current were measured in response to GABAA subunit-selective agonists in cultured human airway smooth muscle cells. Functional relaxation of precontracted guinea pig tracheal rings was assessed in the absence and presence of the α4-subunit-selective GABAA receptor agonists: gaboxadol, taurine, and a novel 8-methoxy imidazobenzodiazepine (CM-D-45). Only messenger RNA encoding the α4- and α5-GABAA receptor subunits was identified in RNA isolated by laser capture dissection from guinea pig and human airway smooth muscle tissues. Activation of airway smooth muscle GABAA receptors with agonists selective for these subunits resulted in appropriate membrane potential changes and chloride currents and promoted relaxation of airway smooth muscle. In conclusion, selective subunit targeting of endogenous airway smooth muscle-specific GABAA receptors may represent a novel therapeutic option for patients in severe bronchospasm.

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