PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Receptors, Adrenergic, beta”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1993

[The effect of therapy with adrenergic beta receptor blockers on myocardial beta adrenergic receptors in children with tetralogy of Fallot].

Seventeen children with tetralogy of Fallot undergoing cardiac surgery were investigated for alteration in myocardial beta-adrenergic receptors (BAR) in dependence on the previous chronic administration with the beta-adrenergic blocker metipranolol. Binding parameters, Bmax (maximal binding capacity) and Kd (dissociation constant), in right ventricular tissue were assessed in direct saturation binding studies using 125I-pindolol. It can be concluded that a) chronic administration of metipranolol to nine patients in usual doses did not change either Bmax or Kd of BAR in the samples of right ventricle, and b) twelve hours interval between last dose of metipranolol and removal of tissue samples is sufficiently long to enable normalization of possible changes in the sensitivity of BAR. This finding is supported by the pot-operative course and the response to dopamine which did not differ in patients treated and untreated with metipranolol in the preoperative period. Thus, our results suggest that there is no apprehension of chronic application of beta-blockers in patients with tetralogy of Fallot which would negatively influence the response to dopamine during the operation and in the postoperative period.

Child, Preschool↗
PubMed2002

Novel signaling pathway through the beta-adrenergic receptor.

beta -Adrenergic receptors transduce signals through the heterotrimeric G protein Galphas to regulate cardiac function. Recently, it has been discovered that Galphas could directly stimulate the Src family tyrosine kinase activity. This novel signaling pathway provides insights into the cAMP-PKA-independent signaling mechanisms used by beta -adrenergic receptors to regulate apoptosis, receptor desensitization, and other physiological functions.

Animals↗
PubMed2006

Pharmacogenetics of the human beta-adrenergic receptors.

The beta-adrenergic receptors (ADRBs) are cell surface receptors that play central roles in the sympathetic nervous system. Pharmacological targeting of two of these receptors, ADRB1 and ADRB2, represents a widely used therapeutic approach for common and important diseases including asthma, hypertension and heart failure. Genetic variation in both ADRB1 and ADRB2 has been linked to both in vitro and clinical disease phenotypes. More recently, interest has shifted to studies that explore potential interaction between variation in ADRBs and medications directed at these important receptors. This paper reviews the current state of knowledge and understanding of ADRB genetic variation and explores the likely direction of future studies in this area.

Humans↗
PubMed2004

Cross-talk of opioid peptide receptor and beta-adrenergic receptor signalling in the heart.

Opioid peptide receptor (OPR) and beta-adrenergic receptor (beta-AR) are well-established members of G-protein-coupled receptor (GPCR) superfamily and are involved in regulating cardiac contractility, energy metabolism, myocyte survival or death. OPRs are typical Gi/Go-coupled receptors and activated by opioid peptides derived from the endorphin, dynorphin and enkephalin families, whereas beta-AR stimulated by catecholamines is the model system for Gs-coupled receptors. While it is widely accepted that beta-AR stimulation serves as the most powerful means to increase cardiac output in response to stress or exercise, we have only begun to appreciate functional roles of OPR stimulation in regulating cardiovascular performance. Cardiovascular regulatory effects of endogenous opioids were initially considered to originate from the central nervous system and involved the pre-synaptic co-release of norepinephrine with enkephalin from sympathetic neuronal terminals in the heart. However, opioid peptides of myocardial origin have been shown to play important roles in local regulation of the heart. Notably, OPR stimulation not only inhibits cardiac excitation-contraction coupling, but also protects the heart against hypoxic and ischemic injury via activation of Gi-mediated signalling pathways. Further, OPRs functionally and physically cross-talk with beta-ARs via multiple hierarchical mechanisms, including heterodimerization of these receptors, counterbalance of functional opposing G protein signalling, and interface at downstream signalling events. As a result, the beta-AR-mediated positive inotropic effect and increase in cAMP are markedly attenuated by OPR activation in isolated cardiomyocytes as well as sympathectomized intact rat hearts. This brief review will focus on the interaction between beta-AR and OPR and its potential physiological and pathophysiological relevance in the heart.

Aging↗
PubMed1993

Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart.

BACKGROUND: In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK). METHODS AND RESULTS: We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters. CONCLUSIONS: In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.

Adult↗
PubMed1991

Comparative rates of desensitization of beta-adrenergic receptors by the beta-adrenergic receptor kinase and the cyclic AMP-dependent protein kinase.

Three separate processes may contribute to rapid beta-adrenergic receptor desensitization: functional uncoupling from the stimulatory guanine nucleotide-binding protein Gs, mediated by phosphorylation of the receptors by two distinct kinases, the specific beta-adrenergic receptor kinase (beta ARK) and the cyclic AMP-dependent protein kinase A (PKA), as well as a spatial uncoupling via sequestration of the receptors away from the cell surface. To evaluate the relative importance and potential role of the various processes in different physiological situations, a kinetic analysis of these three mechanisms was performed in permeabilized A431 epidermoid carcinoma cells. To allow a separate analysis of each mechanism, inhibitors of the various desensitization mechanisms were used: heparin to inhibit beta ARK, the PKA inhibitor peptide PKI to inhibit PKA, and concanavalin A treatment to prevent sequestration. Isoproterenol-induced phosphorylation of beta 2 receptors in these cells by beta ARK occurred with a t1/2 of less than 20 sec, whereas phosphorylation by PKA had a t1/2 of about 2 min. Similarly, beta ARK-mediated desensitization of the receptors proceeded with a t1/2 of less than 15 sec, and PKA-mediated desensitization with a t1/2 of about 3.5 min. Maximal desensitization mediated by the two kinases corresponded to a reduction of the signal-transduction capacity of the receptor/adenylyl cyclase system by about 60% in the case of beta ARK and by about 40% in the case of PKA. Receptor sequestration was much slower (t1/2 of about 10 min) and involved no more than 30% of the cell surface receptors. It is concluded that beta ARK-mediated phosphorylation is the most rapid and quantitatively most important factor contributing to the rapid desensitization. This rapidity of the beta ARK-mediated mechanism makes it particularly well suited to regulate beta-adrenergic receptor function in rapidly changing environments such as the synaptic cleft.

Carcinoma, Squamous Cell↗
PubMed2001

Differential distribution of beta-adrenergic receptor subtypes in blood vessels of knockout mice lacking beta(1)- or beta(2)-adrenergic receptors.

beta-Adrenergic receptors (beta-AR) are essential regulators of cardiovascular homeostasis. In addition to their prominent function in the heart, beta-AR are located on vascular smooth muscle cells, where they mediate vasodilating effects of endogenous catecholamines. In this study, we have investigated in an isometric myograph different types of blood vessels from mice lacking beta(1)- and/or beta(2)-adrenergic receptor subtypes (beta(1)-KO, beta(2)-KO, beta(1)beta(2)-KO). In wild-type mice, isoproterenol induced relaxation of segments from thoracic aorta, carotid, femoral and pulmonary arteries, and portal vein. The relaxant effect of beta-receptor stimulation was absent in femoral and pulmonary arteries from beta(1)-KO mice. In aortic and carotid arteries and in portal veins, the vasodilating effect of isoproterenol was reduced in mice lacking beta(1)- or beta(2)-receptors. However, in these vessels the vasodilating effect was only abolished in double KO mice lacking both beta(1)- and beta(2)-receptors. Vessel relaxation induced by forskolin did not differ between wild-type and KO mice. Similar contributions of beta(1)- and beta(2)-receptors to isoproterenol-induced vasorelaxation were found when vessels from KO mice were compared with wild-type arteries in the presence of subtype-selective beta-receptor antagonists. These studies demonstrate that beta(1)-adrenergic receptors play a dominant role in the murine vascular system to mediate vasodilation. Surprisingly, beta(2)-receptors contribute to adrenergic vasodilation only in a few major blood vessels, suggesting that differential distribution of beta-adrenergic receptor subtypes may play an important role in redirection of tissue perfusion.

Animals↗
PubMed1987

Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein).

The beta-adrenergic receptor kinase is an enzyme, possibly analogous to rhodopsin kinase, that multiply phosphorylates the beta-adrenergic receptor only when it is occupied by stimulatory agonists. Since this kinase may play an important role in mediating the process of homologous, or agonist-specific, desensitization, we investigated the functional consequences of receptor phosphorylation by the kinase and possible analogies with the mechanism of action of rhodopsin kinase. Pure hamster lung beta 2-adrenergic receptor, reconstituted in phospholipid vesicles, was assessed for its ability to mediate agonist-promoted stimulation of the GTPase activity of coreconstituted stimulatory guanine nucleotide-binding regulatory protein. When the receptor was phosphorylated by partially (approximately 350-fold) purified preparations of beta-adrenergic receptor kinase, as much as 80% inactivation of its functional activity was observed. However, the use of more highly purified enzyme preparations led to a dramatic decrease in the ability of phosphorylation to inactivate the receptor such that pure enzyme preparations (approximately 20,000-fold purified) caused only minimal (approximately 1off/- 7%) inactivation. Addition of pure retinal arrestin (48-kDa protein or S antigen), which is involved in enhancing the inactivating effect of rhodopsin phosphorylation by rhodopsin kinase, led to partial restoration of the functional effect of beta-adrenergic receptor kinase-promoted phosphorylation (41 +/- 3% inactivation). These results suggest the possibility that a protein analogous to retinal arrestin may exist in other tissues and function in concert with beta-adrenergic receptor kinase to regulate the activity of adenylate cyclase-coupled receptors.

Animals↗
PubMed2005

Ontogenetic development of mRNA levels and binding sites of hepatic beta-adrenergic receptors in cattle.

Catecholamines regulate glucose metabolism and affect hepatic glucose production mainly through beta2-adrenergic receptors. The hypothesis was tested that gene expression and numbers of hepatic beta-adrenergic receptors in calves are influenced by age. Examined developmental stages included pre-term (P0) and full-term (F0) calves immediately after birth, full-term calves on day 5 of life (F5), and veal calves (VC) at the age of 159 days. Expression of beta1-, beta2-, and beta3-adrenergic receptor mRNA was measured by real-time PCR. Receptor binding was quantified by saturation binding assays using (3H)-CGP-12177 as a ligand. Abundance of mRNA differed among beta-adrenergic subtypes (beta2 > beta1 > beta3; P < 0.01). Beta3-adrenergic receptor mRNA was undetectable in VC. mRNA abundance for beta2-adrenergic receptors was higher (P < 0.05) in VC than P0 and for beta3-adrenergic receptors was higher (P < 0.001) in F5 than P0. Binding studies revealed most binding of (3H)-CGP-12177 to beta2-adrenergic receptors, which were highest in VC (P < 0.001) and higher (P < 0.05) in F5 than P0. Binding sites correlated positively with mRNA levels of beta2-adrenergic receptors (r = 0.67; P < 0.001), with hepatic activities of phosphoenolpyruvate kinase (r = 0.73; P < 0.001) and with pyruvate kinase (r = 0.4; P < 0.05), and with plasma glucose concentrations (r = 0.5; P < 0.01). In conclusion, mRNA of all three beta-adrenergic receptor subtypes were found in liver, with beta2-adrenergic receptors being the dominant subtype. Numbers of beta2-adrenergic receptors increased with age and were mainly regulated at the transcriptional level. Numbers of beta-adrenergic receptors were positively associated with hepatic activities of gluconeogenetic enzymes and with plasma glucose levels, suggesting functional importance.

Aging↗
PubMed1989

Photoaffinity labeling of the guinea pig pulmonary mast cell beta-adrenergic receptor.

Beta-adrenergic agonists can prevent mediator release from guinea pig pulmonary mast cells. By pharmacologic characterization, this response is mediated through a beta-2 receptor. Structural characterization of this receptor on the lung mast cell, however, has been limited by methods for isolation of this pulmonary cell. In this study, the guinea pig lung mast cell was isolated to greater than 90% purity, and its beta-adrenergic receptor identified by photoaffinity labeling with [125I]iodoazidobenzylpindolol (125IABP) and separation of membrane proteins by SDS-PAGE. We found the guinea pig pulmonary mast cell beta-adrenergic receptor to electrophorese as a heterogeneous protein between 68 and 116 kD. Photoaffinity labeling with 125IABP was protectable by alprenolol and isoproterenol but not by phentolamine and norepinephrine. Using subtype-selective compounds, the pulmonary mast cell receptor was established to be of a beta-2 subtype. This is the first report of the structural identification of a lung mast cell beta-adrenergic receptor and the first report of a beta-adrenergic receptor of approximately 100 kD in mass. This mast cell receptor is considerably larger than the 65 kD beta-adrenergic receptors that have been identified in whole lung and other tissues. Data we have obtained using Northern blot analysis of mast cell RNA suggest a protein message of 45 kD for this beta-adrenergic receptor and a high degree of glycosylation most likely accounts for the large molecular size observed.

Affinity Labels↗
PubMed1988

Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists.

Beta-adrenergic receptors were characterized in human fat cell membranes using 125I-labeled cyanopindolol (125I-labeled CYP) and highly selective beta 1-antagonists. The iodinated radioligand bound saturably and specifically to a single class of high affinity binding sites. The number of binding sites determined with 125I-labeled CYP closely agreed with that determined with two other tritiated radioligands: [3H]dihydroalprenolol and [3H]CGP-12,177. Since 125I-labeled CYP does not discriminate between beta 1- and beta 2-adrenoceptors, the densities of the two receptor subtypes were determined from the competition curves of 125I-labeled CYP by highly selective beta 1-antagonists (bisoprolol, ICI-89,406, CGP-20,712A, and LK-204,545). Moreover, in order to enable correlation with binding data, the regulation of adenylate cyclase activity and of lipolysis was tested with various beta-agonist and antagonist compounds. The results obtained on fat cell membranes from abdominal subcutaneous adipose tissue demonstrated the following. 1) 125I-labeled CYP represents a valuable tool for the quantification and the delineation of beta-receptor subtypes. 2) The presence of sodium ions in binding buffers causes a modification of the affinity of beta-sites for some beta-antagonists. 3) The human fat cell beta adrenergic receptor population defined by nonselective radioligands is composed of two subtypes that can be interpreted in terms of classic beta 1- and beta 2-adrenergic receptor subtypes as assessed by competition studies with highly selective antagonists; beta 2-sites are predominant (60-70% of 125I-labeled CYP sites) in the adipocytes of slightly overweight women. 4) Results support the idea that beta 1- as well as beta 2-adrenergic receptors are coupled with adenylate cyclase and involved in the induction of lipolysis. 5) The results focus on the interest in some beta 2-agonist drugs (zinterol, clenbuterol) as partial inductors of lipolysis, with the lipolytic efficacies of these compounds being well correlated with their efficacies at 125I-labeled CYP sites.

Adenylyl Cyclases↗
PubMed2005

Interactive effects between polymorphisms in the beta-adrenergic receptors and longitudinal changes in obesity.

We assessed interactions between polymorphisms in the beta-adrenergic receptor genes and longitudinal changes in obesity from childhood to adulthood using longitudinal data collected over a 24-year period from 1973 to 1996. Sex- and age-stratified analyses using random coefficients models were used to examine gene-gene interaction effects on obesity measures in 1179 African-American and white men and women (71% white, 57% women). Suggestive evidence for an interaction (p = 0.022) between the beta1- and beta2-adrenergic receptors was observed in men for longitudinal change in BMI. Men with Gly/Gly genotypes for both the beta1 and beta2 receptors showed significant increases (approximately 0.6%/yr) in BMI from childhood to adulthood. Women showed suggestive evidence for an interaction (p = 0.035) between the beta1- and beta3-adrenergic receptors for change over time in BMI. Women with Gly/Gly genotypes at the beta1-receptor and carrying at least one beta3-Arg allele showed notable increases in BMI. The regulation of lipolysis and development of obesity differ markedly between men and women and may be influenced by genetic polymorphisms, which contribute to the efficiency of the beta-adrenergic receptors, and hormonal effects on adrenergic receptor activity.

Black People↗
PubMed1991

Beta-adrenergic receptors and m-cholinergic receptors in human lung. Findings following in vivo and in vitro exposure to the beta-adrenergic receptor agonist, terbutaline.

In order to investigate whether treatment with terbutaline (1 mg subcutaneously) in patients with bronchial obstruction is accompanied by changes in the densities of receptors of the autonomic nervous system, beta-adrenergic receptors or m-cholinergic receptors were measured in membrance preparations of human peripheral lung tissue from patients undergoing lung resection for bronchial carcinoma. The density of beta-adrenergic receptors and mononuclear leukocytes (MNLs) of treated and untreated patients and beta-adrenergic receptors and m-cholinergic receptors in lung strips from the same patients exposed to terbutaline in vitro were studied for comparison. In patients, treatment with terbutaline did not have any effect on human lung beta-adrenergic receptors and m-cholinergic receptors, whereas a 57 percent decline was measured in the number of beta-receptors on MNLs of the very same patients. In contrast, in vitro exposure of human peripheral lung strips to terbutaline (100 mumol/L for 36 hours) evoked a time-dependent and concentration-dependent decline of 46 percent in beta-adrenergic receptors. Again, there was no change in the number of m-cholinergic receptors. The antagonist affinities, as judged from the KD values, did not differ under either condition. We concluded that lung beta-adrenergic receptors are subject to down-regulation when exposed to agonists in vitro. This down-regulation in the human lung is not accompanied by alterations in m-cholinergic receptors. Down-regulation of beta-adrenergic receptors or up-regulation of m-cholinergic receptors appears not to play a role in the proposed tolerance to beta-adrenergic receptor agonist treatment in clinical situations. The reduction of beta-adrenergic receptors in MNLs provides evidence that treatment with terbutaline was sufficient to affect beta-adrenergic receptors in vivo in certain cell types but also shows that alterations in blood cells do not necessarily reflect the situation in the lung.

Aged↗
PubMed2003

Detection and quantification of mRNA expression of alpha- and beta-adrenergic receptor subtypes in the mammary gland of dairy cows.

Adrenergic receptors are pharmacologically classified into the receptor types alpha(1), alpha(2), beta(1), beta(2), and beta(3). Structural differences and varying affinities in radioligand binding studies lead to a further classification of alpha(1)- and alpha(2)-receptors into subtypes which are termed alpha(1A) (formerly alpha(1C)), alpha(1B), and alpha(1D) (formerly alpha(1AD)), and alpha(2AD), alpha(2B), and alpha(2C), respectively. mRNA expression of all but one alpha-adrenergic receptor subtypes and of all beta-adrenergic receptor types was measured quantitatively in total RNA extracted from mammary tissue of 10 lactating dairy cows by real-time reverse transcription (RT) polymerase chain reaction (PCR). mRNA expression of alpha(1)-adrenergic receptors was highest for the alpha(1A)-subtype followed by alpha(1B), whereas the alpha(1D)-subtype could not be detected. The highest mRNA expression of alpha(2)-adrenergic receptors was found for the alpha(2AD)-subtype, followed by alpha(2B) and alpha(2C). Within the beta-adrenergic receptors, the beta(2)-receptor type was most highly expressed, followed by beta(1) and beta(3). In conclusion, eight of nine adrenergic receptors classified to date were detected and relatively quantified in the mammary gland of dairy cows.

Animals↗
PubMed1986

Evidence for tyrosine at the ligand binding center of beta-adrenergic receptors.

Beta 1- and beta 2-adrenergic receptor radioligand antagonist binding activities in plasma membrane preparations from mammalian lung, as well as amphibian and avian red blood cells, have been shown to be inactivated by agents which specifically alkylate tyrosine. In membrane preparations, protection against inactivation was afforded by both agonists and antagonists. In soluble purified preparations, antagonists but not agonists protected against inactivation. These results suggest that tyrosine is located at or near the ligand binding site of both beta 1- and beta 2-adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1986

Down-regulation of serotonin2, but not of beta-adrenergic receptors during chronic treatment with amitriptyline is independent of stimulation of serotonin2 and beta-adrenergic receptors.

Antidepressant drugs down-regulate beta-adrenergic, alpha 2-adrenergic and serotonergic 5-HT2 receptors with a time course that parallels their clinical efficacy, i.e. chronic administration is required (Crews and Smith, 1978; Svensson and Usdin, 1978; Banerjee, Kung, Riggi and Chanda, 1979; Bergstrom and Keller, 1979; Peroutka and Snyder, 1980). In the present study, it was found that the 5-HT2 receptor antagonist, nefazadone (50 mg/kg per day) did not prevent the downregulation of 5-HT2 receptors in the cerebral cortex produced by amitriptyline (10 mg/kg per day), when administered for 3 weeks. Moreover, treatment with nefazadone (50 mg/kg per day) alone for 3 weeks decreased binding to 5-HT2 receptors in cerebral cortex. In contrast, administration of propranolol, the beta receptor antagonist, (10 mg/kg per day) with amitriptyline (10 mg/kg per day) for 3 weeks prevented the down-regulation of beta receptors, but did not alter the decrease in binding to 5-HT2 receptors. In addition, the depletion of central stores of norepinephrine and serotonin by a 4-day treatment with reserpine (5 mg/kg per day) increased binding to beta receptors in the cerebral cortex and hippocampus, but did not affect binding to 5-HT2 receptors in either region. These results suggest that the 5-HT2 receptor is not down-regulated by direct stimulation by serotonin agonists and that the down-regulation of 5-HT2 receptors by amitriptyline is independent of down-regulation of beta-adrenergic receptors.

Amitriptyline↗
PubMed2005

Interdependency of beta-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport.

Beta-adrenergic receptors (betaAR) regulate active Na+ transport in the alveolar epithelium and accelerate clearance of excess airspace fluid. Accumulating data indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) is important for upregulation of the active ion transport that is needed to maintain alveolar fluid homeostasis during pulmonary edema. We hypothesized that betaAR regulation of alveolar active transport may be mediated via a CFTR dependent pathway. To test this hypothesis we used a recombinant adenovirus that expresses a human CFTR cDNA (adCFTR) to increase CFTR function in the alveolar epithelium of normal rats and mice. Alveolar fluid clearance (AFC), an index of alveolar active Na+ transport, was 92% greater in CFTR overexpressing lungs than controls. Addition of the Cl- channel blockers NPPB, glibenclamide, or bumetanide and experiments using Cl- free alveolar instillate solutions indicate that the accelerated AFC in this model is due to increased Cl- channel function. Conversely, CFTR overexpression in mice with no beta1- or beta2-adrenergic receptors had no effect on AFC. Overexpression of a human beta2AR in the alveolar epithelium significantly increased AFC in normal mice but had no effect in mice with a non-functional human CFTR gene (Deltaphi508 mutation). These studies indicate that upregulation of alveolar CFTR function speeds clearance of excess fluid from the airspace and that CFTRs effect on active Na+ transport requires the betaAR. These studies reveal a previously undetected interdependency between CFTR and betaAR that is essential for upregulation of active Na+ transport and fluid clearance in the alveolus.

Animals↗