HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A corrigendum has been published All Versions of this Article: 289/2/L349    most recent 00134.2004v1 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 (2) Citing Articles via Google Scholar Google Scholar Articles by Maron, M. B. Articles by Walro, J. M. Search for Related Content PubMed PubMed Citation Articles by Maron, M. B. Articles by Walro, J. M.

PKA delivery to the distal lung air spaces increases alveolar liquid clearance after isoproterenol-induced alveolar epithelial PKA desensitization

Departments of ¹Physiology and Pharmacology and ²Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio

Submitted 12 April 2004 ; accepted in final form 19 April 2005

Isoproterenol (Iso) infusion for 48 h in rats decreases the ability of -adrenoceptor (-AR) agonists to increase alveolar liquid clearance (ALC). An impairment in protein kinase A (PKA) function appears to be critical in producing the desensitized ALC response. To test this hypothesis, we used a novel protein delivery reagent (Chariot, Active Motif) to deliver either the PKA catalytic subunit or the PKA holoenzyme to the distal lung epithelium of Iso-infused rats (400 µg·kg^–1·h^–1, 48 h). After this infusion, ALC was measured by mass balance over 2 h. ALC in Iso-infused rats was 27.9% (SD 5.8) of instilled volume absorbed. Delivery of the catalytic PKA subunit to Iso-infused rats increased ALC to 47.7% (SD 8.9) (P < 0.05). ALC in Iso-infused rats delivered the inactive PKA holoenzyme [29.6% (SD 2.5)] was not increased above baseline values. Subsequent holoenzyme activation by intravenous infusion of the stable cAMP analog Sp-8-Bromo-cAMPS increased ALC to 41.7% (SD 8.8) (P < 0.05). Immunohistochemical localization of Chariot-delivered PKA revealed staining in the alveolar and distal airway epithelium. These data indicate that protein delivery reagents can be used to rapidly deliver biologically active proteins to the distal lung epithelium and that PKA desensitization may be an important rate-limiting event in the development of Iso-induced desensitization of the alveolar epithelial -AR signaling pathway.

pulmonary edema; -adrenoceptor signaling pathway; protein kinase A; protein delivery reagents

This article has been cited by other articles:

				C. J. Clarke, S. Forman, J. Pritchett, V. Ohanian, and J. Ohanian Phospholipase C-{delta}1 modulates sustained contraction of rat mesenteric small arteries in response to noradrenaline, but not endothelin-1 Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H826 - H834. [Abstract] [Full Text] [PDF]

				M. B. Maron, H. G. Folkesson, S. M. Stader, and C. M. Hodnichak Impaired alveolar liquid clearance after 48-h isoproterenol infusion spontaneously recovers by 96 h of continuous infusion Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L252 - L256. [Abstract] [Full Text] [PDF]

				H. G. Folkesson and M. A. Matthay Alveolar Epithelial Ion and Fluid Transport: Recent Progress Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 10 - 19. [Full Text] [PDF]