ArticleBritish journal of pharmacology2001
Evidence that the anti-spasmogenic effect of the beta-adrenoceptor agonist, isoprenaline, on guinea-pig trachealis is not mediated by cyclic AMP-dependent protein kinase.
Article in British journal of pharmacology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 42 citations in OpenAlex.
- Antispasmodic, cardioprotective and blood-pressure lowering properties ofJournal of traditional and complementary medicine · 2024Article
- G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.Pharmacological reviews · 2020Review
- Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice.Respiratory research · 2019Article
- Selective inhibition of histamine-evoked CaCell calcium · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Prostaglandin EMolecular pharmacology · 2017Article
- The effect of cyclic nucleotide analog drugs on the mediators release from basophils.Advanced biomedical research · 2015Article
- The role of adenylyl cyclase isoform 6 in β-adrenoceptor signalling in murine airways.British journal of pharmacology · 2015Article
- β-Agonist-mediated relaxation of airway smooth muscle is protein kinase A-dependent.The Journal of biological chemistry · 2014Article
- The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle.Respiratory research · 2013Article
- cAMP regulation of airway smooth muscle function.Pulmonary pharmacology & therapeutics · 2013Review
- Adenylyl cyclase 2 selectively couples to E prostanoid type 2 receptors, whereas adenylyl cyclase 3 is not receptor-regulated in airway smooth muscle.The Journal of pharmacology and experimental therapeutics · 2012Article
- Epac as a novel effector of airway smooth muscle relaxation.Journal of cellular and molecular medicine · 2011Article
- Human bronchial smooth muscle cells express adenylyl cyclase isoforms 2, 4, and 6 in distinct membrane microdomains.The Journal of pharmacology and experimental therapeutics · 2011Article
- Anti-mitogenic effects of β-agonists and PGE2 on airway smooth muscle are PKA dependent.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2011Article
- Regulation of heterotrimeric G protein signaling in airway smooth muscle.Proceedings of the American Thoracic Society · 2008Review
- Acute impairment of contractile responses by 17beta-estradiol is cAMP and protein kinase G dependent in vascular smooth muscle cells of the porcine coronary arteries.British journal of pharmacology · 2005Article
- Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13 generation from human basophils.British journal of pharmacology · 2004Article
- Signaling and regulation of G protein-coupled receptors in airway smooth muscle.Respiratory research · 2003Review
- Protein kinase A-independent responses to beta-adrenoceptor agonists.British journal of pharmacology · 2001Article
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6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. The spasmolytic and anti-spasmogenic activity of beta-adrenoceptor agonists on airways smooth muscle is thought to involve activation of the cyclic AMP/cyclic AMP-dependent protein kinase (PKA) cascade. Here we have tested the hypothesis that PKA mediates the anti-spasmogenic activity of isoprenaline and other cyclic AMP-elevating agents in guinea-pig isolated trachea by utilizing a number of cell permeant cyclic AMP analogues that act as competitive 'antagonists' of PKA. 2. Anion-exchange chromatography of guinea-pig tracheae resolved two peaks of PKA activity that corresponded to the type I ( approximately 5%) and type II ( approximately 93%) isoenzymes. 3. Pre-treatment of tracheae with zardaverine (30 microM), vasoactive intestinal peptide (VIP) (1 microM) and the non-selective activator of PKA, Sp-8-CPT-cAMPS (10 microM), produced a non-parallel rightwards shift in the concentration-response curves that described acetylcholine (ACh)-induced tension generation. The type II-selective PKA inhibitor, Rp-8-CPT-cAMPS (300 microM), abolished this effect. 4. Pre-treatment of tracheae with Sp-8-Br-PET-cGMPS (30 microM) produced a non-parallel rightwards shift of the concentration-response curves that described ACh-induced tension generation. The selective cyclic GMP-dependent protein kinase (PKG) inhibitor, Rp-8-pCPT-cGMPS (300 microM), abolished this effect. 5. Pre-treatment of tracheae with isoprenaline (1 microM) produced a 10 fold shift to the right of the ACh concentration-response curve by a mechanism that was unaffected by Rp-8-Br-cAMPS (300 microM, selective inhibitor of type I PKA), Rp-8-CPT-cAMPS (300 microM) and Rp-8-pCPT-cGMPS (300 microM). 6. We conclude that the anti-spasmogenic activity of Sp-8-CPT-cAMPS, zardaverine and VIP in guinea-pig trachea is attributable to activation of the cyclic AMP/PKA cascade whereas isoprenaline suppresses ACh-induced contractions by a mechanism(s) that is independent of PKA and PKG.
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