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Edward J Filardo - One of the best experts on this subject based on the ideXlab platform.
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retrograde transport of the transmembrane estrogen Receptor g protein coupled Receptor 30 gpr30 gper from the plasma membrane towards the nucleus
Steroids, 2011Co-Authors: Shibin Cheng, Carl T Graeber, Jeffrey A Quinn, Edward J FilardoAbstract:Abstract G-protein-coupled Receptor 30 (GPR30/GPER) belongs to the seven transmembrane Receptor (7TMR) superfamily, the most common class of surface Receptor with approximately 800 known members. GPER promotes estrogen binding and rapid signaling via membrane-associated enzymes resulting in increased cAMP and release of heparan bound epidermal growth factor (proHB-EGF) from breast cancer cells. However, GPER is predominately localized intracellularly in breast cancer cells with minor amounts of Receptor on the cell surface, an observation that has caused some controversy regarding its potential role as a plasma membrane estrogen Receptor. Using the widely employed approach of tracking recombinant 7TMRs by surface labeling live cells, we have begun to characterize and compare the endocytic fate of GPER to other similarly labeled 7TMRs. Upon ectopic expression in human embryonic kidney HEK-293 cells, functional GPER is generated as these cells acquire the capacity to stimulate cAMP and activate cyclic AMP responsive binding protein in response to estradiol-17 beta stimulation. GPER is detectable on the cell surface by immunofluorescent analysis using HA-specific antibodies, albeit the bulk of the Receptor is located intracellularly. Like β1AR (beta 1 Adrenergic Receptor) and CXCR4 (C-X-C chemokine Receptor 4), GPER exits the plasma membrane via clathrin-coated pits and enters early endosomes. Interestingly, GPER has a destination that is uncommon among 7TMRs, as it accumulates in a perinuclear compartment. Like many 7TMRs (approximately one-third), GPER trafficking from the plasma membrane is constitutive (occurs in the absence of agonist). However, its route of intracellular trafficking is highly unusual, as 7TMRs typically recycle to the plasma membrane (e.g. β1AR) or are degraded in lysosomes (e.g. CXCR4). The accumulation of GPER in the perinuclear space and its possible significance for attenuating estrogen action via this newly recognized membrane estrogen Receptor is discussed herein.
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retrograde transport of the transmembrane estrogen Receptor g protein coupled Receptor 30 gpr30 gper from the plasma membrane towards the nucleus
Steroids, 2011Co-Authors: Shibin Cheng, Carl T Graeber, Jeffrey A Quinn, Edward J FilardoAbstract:Abstract G-protein-coupled Receptor 30 (GPR30/GPER) belongs to the seven transmembrane Receptor (7TMR) superfamily, the most common class of surface Receptor with approximately 800 known members. GPER promotes estrogen binding and rapid signaling via membrane-associated enzymes resulting in increased cAMP and release of heparan bound epidermal growth factor (proHB-EGF) from breast cancer cells. However, GPER is predominately localized intracellularly in breast cancer cells with minor amounts of Receptor on the cell surface, an observation that has caused some controversy regarding its potential role as a plasma membrane estrogen Receptor. Using the widely employed approach of tracking recombinant 7TMRs by surface labeling live cells, we have begun to characterize and compare the endocytic fate of GPER to other similarly labeled 7TMRs. Upon ectopic expression in human embryonic kidney HEK-293 cells, functional GPER is generated as these cells acquire the capacity to stimulate cAMP and activate cyclic AMP responsive binding protein in response to estradiol-17 beta stimulation. GPER is detectable on the cell surface by immunofluorescent analysis using HA-specific antibodies, albeit the bulk of the Receptor is located intracellularly. Like β1AR (beta 1 Adrenergic Receptor) and CXCR4 (C-X-C chemokine Receptor 4), GPER exits the plasma membrane via clathrin-coated pits and enters early endosomes. Interestingly, GPER has a destination that is uncommon among 7TMRs, as it accumulates in a perinuclear compartment. Like many 7TMRs (approximately one-third), GPER trafficking from the plasma membrane is constitutive (occurs in the absence of agonist). However, its route of intracellular trafficking is highly unusual, as 7TMRs typically recycle to the plasma membrane (e.g. β1AR) or are degraded in lysosomes (e.g. CXCR4). The accumulation of GPER in the perinuclear space and its possible significance for attenuating estrogen action via this newly recognized membrane estrogen Receptor is discussed herein.
Naohiro Komura - One of the best experts on this subject based on the ideXlab platform.
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Randomized controlled trial of landiolol, a short-acting Beta-1 Adrenergic Receptor blocker, illustrating changes in high-molecular weight adiponectin levels after elective percutaneous coronary intervention
Heart and Vessels, 2020Co-Authors: Masayoshi Kiyokuni, Masaaki Konishi, Kiwamu Iwata, Naoki Nakayama, Naohiro Komura, Yusuke Saigusa, Teruyasu Sugano, Tomoaki Ishigami, Toshiyuki Ishikawa, Takeharu YamanakaAbstract:Adiponectin (APN) has cardioprotective properties and bisoprolol has been reported to increase myocardial APN expression and reduce myocardial damage. Administration of landiolol, which has a higher cardio-selectivity and shorter half-life than bisoprolol, during the percutaneous coronary intervention (PCI) may increase serum APN and high-molecular weight (HMW)-APN, an active form of APN, in patients with stable angina pectoris (SAP). We recruited 70 patients with SAP and randomized them to intravenous landiolol during PCI ( N = 35) or control group ( N = 35). The primary endpoint was serum APN and HMW-APN level 3 days after PCI. There was no difference in the primary endpoint between the landiolol and control groups (8.93 ± 5.24 vs. 10.18 ± 5.81 μg/mL, p = 0.35 and 3.36 ± 2.75 vs. 4.28 ± 3.13 μg/mL, p = 0.20) for APN and HMW-APN levels, respectively. APN and HMW-APN level were significantly decreased 1 day after PCI [−0.55 ± 0.92 μg/mL (9.87–9.32 μg/mL), p
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Beneficial effect of early infusion of landiolol, a very short-acting Beta-1 Adrenergic Receptor blocker, on reperfusion status in acute myocardial infarction
International Journal of Cardiology, 2016Co-Authors: Masayoshi Kiyokuni, Masaaki Konishi, Kentaro Sakamaki, Chika Kawashima, Masatoshi Narikawa, Kiwamu Iwata, Sakie Tomari, Naoki Nakayama, Naohiro KomuraAbstract:Abstract Background An early IV beta blocker during primary percutaneous coronary intervention (PCI) has been shown to reduce infarct size in ST-segment elevation acute myocardial infarction (STEMI), although the underlying mechanism is unknown. The aim of this study was to investigate the efficacy of early infusion of landiolol, the short-acting Beta-1 Adrenergic Receptor blocker, on the reperfusion status in a STEMI. Methods We conducted a prospective, single-group trial of landiolol during the primary PCI for a STEMI. Landiolol was started intravenously just before reperfusion. The reperfusion status and outcomes in 55 treated patients were compared with those in 60 historical controls treated without landiolol. The optimal reperfusion was assessed by an ST-segment resolution (STR), coronary flow, and myocardial brush grade (MBG) after reperfusion. Results Patients in the landiolol group achieved a higher rate of an STR (64% vs. 42%, p =0.023) and MBG 2/3 (64% vs. 45%, p =0.045), whereas coronary flow was comparable between the two groups. A multivariate analysis showed that landiolol use was an independent predictor of an STR (odds ratio 2.99, 95% confidence interval 1.25–7.16, p =0.014). The incidence of non-sustained ventricular tachycardia (27% vs. 50%, p =0.014), hypotension (15% vs. 32%, p =0.046), and progression to Killip class grade III or IV (0% vs. 10%, p =0.028) were lower in the landiolol group. Conclusion Early infusion of landiolol during the primary PCI was associated with optimal reperfusion and a lower incidence of adverse events in comparison with the control group.
Masayoshi Kiyokuni - One of the best experts on this subject based on the ideXlab platform.
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Randomized controlled trial of landiolol, a short-acting Beta-1 Adrenergic Receptor blocker, illustrating changes in high-molecular weight adiponectin levels after elective percutaneous coronary intervention
Heart and Vessels, 2020Co-Authors: Masayoshi Kiyokuni, Masaaki Konishi, Kiwamu Iwata, Naoki Nakayama, Naohiro Komura, Yusuke Saigusa, Teruyasu Sugano, Tomoaki Ishigami, Toshiyuki Ishikawa, Takeharu YamanakaAbstract:Adiponectin (APN) has cardioprotective properties and bisoprolol has been reported to increase myocardial APN expression and reduce myocardial damage. Administration of landiolol, which has a higher cardio-selectivity and shorter half-life than bisoprolol, during the percutaneous coronary intervention (PCI) may increase serum APN and high-molecular weight (HMW)-APN, an active form of APN, in patients with stable angina pectoris (SAP). We recruited 70 patients with SAP and randomized them to intravenous landiolol during PCI ( N = 35) or control group ( N = 35). The primary endpoint was serum APN and HMW-APN level 3 days after PCI. There was no difference in the primary endpoint between the landiolol and control groups (8.93 ± 5.24 vs. 10.18 ± 5.81 μg/mL, p = 0.35 and 3.36 ± 2.75 vs. 4.28 ± 3.13 μg/mL, p = 0.20) for APN and HMW-APN levels, respectively. APN and HMW-APN level were significantly decreased 1 day after PCI [−0.55 ± 0.92 μg/mL (9.87–9.32 μg/mL), p
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Beneficial effect of early infusion of landiolol, a very short-acting Beta-1 Adrenergic Receptor blocker, on reperfusion status in acute myocardial infarction
International Journal of Cardiology, 2016Co-Authors: Masayoshi Kiyokuni, Masaaki Konishi, Kentaro Sakamaki, Chika Kawashima, Masatoshi Narikawa, Kiwamu Iwata, Sakie Tomari, Naoki Nakayama, Naohiro KomuraAbstract:Abstract Background An early IV beta blocker during primary percutaneous coronary intervention (PCI) has been shown to reduce infarct size in ST-segment elevation acute myocardial infarction (STEMI), although the underlying mechanism is unknown. The aim of this study was to investigate the efficacy of early infusion of landiolol, the short-acting Beta-1 Adrenergic Receptor blocker, on the reperfusion status in a STEMI. Methods We conducted a prospective, single-group trial of landiolol during the primary PCI for a STEMI. Landiolol was started intravenously just before reperfusion. The reperfusion status and outcomes in 55 treated patients were compared with those in 60 historical controls treated without landiolol. The optimal reperfusion was assessed by an ST-segment resolution (STR), coronary flow, and myocardial brush grade (MBG) after reperfusion. Results Patients in the landiolol group achieved a higher rate of an STR (64% vs. 42%, p =0.023) and MBG 2/3 (64% vs. 45%, p =0.045), whereas coronary flow was comparable between the two groups. A multivariate analysis showed that landiolol use was an independent predictor of an STR (odds ratio 2.99, 95% confidence interval 1.25–7.16, p =0.014). The incidence of non-sustained ventricular tachycardia (27% vs. 50%, p =0.014), hypotension (15% vs. 32%, p =0.046), and progression to Killip class grade III or IV (0% vs. 10%, p =0.028) were lower in the landiolol group. Conclusion Early infusion of landiolol during the primary PCI was associated with optimal reperfusion and a lower incidence of adverse events in comparison with the control group.
Hideo Mitamura - One of the best experts on this subject based on the ideXlab platform.
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autoimmunity against the second extracellular loop of beta1 Adrenergic Receptors induces early afterdepolarization and decreases in k channel density in rabbits
Journal of the American College of Cardiology, 2004Co-Authors: Yukiko Fukuda, Shunichiro Miyoshi, Kojiro Tanimoto, Kenichi Oota, Kana Fujikura, Michikado Iwata, Akiyasu Baba, Yoko Hagiwara, Tsutomu Yoshikawa, Hideo MitamuraAbstract:Abstract Objectives We sought to define the electrophysiologic property of the rabbit heart associated with autoimmunity against the second extracellular loop of the beta 1 -Adrenergic Receptor. Background Sudden death of patients with cardiomyopathy, probably due to lethal ventricular arrhythmias, can be predicted by the presence of autoantibodies against the second extracellular loop of the beta 1 -Adrenergic Receptor. Methods Rabbits were immunized by repetitive subcutaneous administration of a synthetic peptide corresponding to the second extracellular loop of beta 1 -Adrenergic Receptors (beta group; n = 30) for a mean of 4.2 months. Control rabbits received only vehicle (control group; n = 30). Results One of the rabbits in the beta group died suddenly during the observation period, but none of the control animals died. The prevalence of sustained ventricular tachycardia was significantly higher in the beta group (beta: 4 of 27 vs. control: 0 of 30), and a standard microelectrode experiment revealed prolongation of the action potential duration (APD) in the right ventricular papillary muscle (beta: 156 ± 5 ms vs. control: 131 ± 4 ms; p to1 ) (−43%) and slowly activated delayed rectifier current (I Ks ) densities (−33%), whereas the inward-rectifying K current (I K1 ) and rapidly activated delayed rectifier current (I Kr ) densities remained unchanged. Conclusions Long-term immunization against the second extracellular loop of the beta 1 -Adrenergic Receptor caused EAD and APD prolongation and decreased the K-channel density, suggesting that an arrhythmic substrate via autoimmune mechanisms is present in cardiomyopathic patients who have autoantibodies directed against the Receptors.
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Autoimmunity against the second extracellular loop of beta1-Adrenergic Receptors induces early afterdepolarization and decreases in K-channel density in rabbits
Journal of the American College of Cardiology, 2004Co-Authors: Yukiko Fukuda, Shunichiro Miyoshi, Kojiro Tanimoto, Kenichi Oota, Kana Fujikura, Michikado Iwata, Akiyasu Baba, Yoko Hagiwara, Tsutomu Yoshikawa, Hideo MitamuraAbstract:Abstract Objectives We sought to define the electrophysiologic property of the rabbit heart associated with autoimmunity against the second extracellular loop of the beta 1 -Adrenergic Receptor. Background Sudden death of patients with cardiomyopathy, probably due to lethal ventricular arrhythmias, can be predicted by the presence of autoantibodies against the second extracellular loop of the beta 1 -Adrenergic Receptor. Methods Rabbits were immunized by repetitive subcutaneous administration of a synthetic peptide corresponding to the second extracellular loop of beta 1 -Adrenergic Receptors (beta group; n = 30) for a mean of 4.2 months. Control rabbits received only vehicle (control group; n = 30). Results One of the rabbits in the beta group died suddenly during the observation period, but none of the control animals died. The prevalence of sustained ventricular tachycardia was significantly higher in the beta group (beta: 4 of 27 vs. control: 0 of 30), and a standard microelectrode experiment revealed prolongation of the action potential duration (APD) in the right ventricular papillary muscle (beta: 156 ± 5 ms vs. control: 131 ± 4 ms; p to1 ) (−43%) and slowly activated delayed rectifier current (I Ks ) densities (−33%), whereas the inward-rectifying K current (I K1 ) and rapidly activated delayed rectifier current (I Kr ) densities remained unchanged. Conclusions Long-term immunization against the second extracellular loop of the beta 1 -Adrenergic Receptor caused EAD and APD prolongation and decreased the K-channel density, suggesting that an arrhythmic substrate via autoimmune mechanisms is present in cardiomyopathic patients who have autoantibodies directed against the Receptors.
Suleiman W. Bahouth - One of the best experts on this subject based on the ideXlab platform.
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SAP97 Controls the Trafficking and Resensitization of the Beta-1-Adrenergic Receptor through Its PDZ2 and I3 Domains
PloS one, 2013Co-Authors: Mohammed M. Nooh, Anjaparavanda P. Naren, Sung Jin Kim, Yang Kevin Xiang, Suleiman W. BahouthAbstract:Previous studies have determined that the type-1 PDZ sequence at the extreme carboxy-terminus of the s1-Adrenergic Receptor (s1-AR) binds SAP97 and AKAP79 to organize a scaffold involved in trafficking of the s1-AR. In this study we focused on characterizing the domains in SAP97 that were involved in recycling and resensitization of the s1-AR in HEK-293 cells. Using a SAP97 knockdown and rescue strategy, we determined that PDZ-deletion mutants of SAP97 containing PDZ2 rescued the recycling and resensitization of the s1-AR. Among the three PDZs of SAP97, PDZ2 displayed the highest affinity in binding to the s1-AR. Expression of isolated PDZ2, but not the other PDZs, inhibited the recycling of the s1-AR by destabilizing the macromolecular complex involved in trafficking and functional resensitization of the s1-AR. In addition to its PDZs, SAP97 contains other protein interacting domains, such as the I3 sequence in the SRC homology-3 (SH3) domain, which binds to AKAP79. Deletion of I3 from SAP97 (ΔI3-SAP97) did not affect the binding of SAP97 to the s1-AR. However, ΔI3-SAP97 could not rescue the recycling of the s1-AR because it failed to incorporate AKAP79/PKA into the SAP97-s1-AR complex. Therefore, bipartite binding of SAP97 to the s1-AR and to AKAP79 is necessary for SAP97-mediated effects on recycling, externalization and functional resensitization of the s1-AR. These data establish a prominent role for PDZ2 and I3 domains of SAP97 in organizing the s1-Adrenergic receptosome involved in connecting the s1-AR to trafficking and signaling networks.
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Identification of a glucocorticoid repressor domain in the rat beta 1-Adrenergic Receptor gene.
Receptors & signal transduction, 1996Co-Authors: Suleiman W. Bahouth, Edwards A. Park, Beauchamp M, Cui X, Craig C. MalbonAbstract:The expression of the gene encoding the rat beta 1-Adrenergic Receptor is suppressed by glucocorticoids (Kiely et al., 1994). Within the 3.2-kb 5'-flanking region of the promoter, two potential glucocorticoid response elements (GREs) at -950 and -2791 relative to the translational ATG were identified. Characterization of the glucocorticoid-responsive sequences in the 5'-flanking region of the beta 1-Adrenergic Receptor gene was explored in rat C6 glioma cells and human HepG2 hepatoma cells using transient expression of beta 1-Adrenergic Receptor-luciferase fusion genes. The ability of glucocorticoids to suppress luciferase expression was not altered when the most 5'-localized GRE was deleted. Deleting the potential GRE at -950, in contrast, abolished glucocorticoid-induced suppression of the beta 1-Adrenergic Receptor-luciferase gene transcription. A 25-bp element containing the GRE sequence between nucleotides -950 and -926 confers glucocorticoid-dependent inhibition of transcription to a neutral promoter. Gel mobility shift assays with the alpha-subunit of the human glucocorticoid Receptor (hGR alpha) expressed in reticulocyte lysates demonstrated specific binding to the 25-bp sequence harboring the putative GRE. We report an inhibitory GRE in the promoter of the rat beta 1-Adrenergic Receptor gene that is conserved among the rat, human, and mouse genes.
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Enhanced desensitization and phosphorylation of the beta 1-Adrenergic Receptor in rat adipocytes by peroxovanadate.
Molecular pharmacology, 1996Co-Authors: Suleiman W. Bahouth, Yesim Gökmen-polar, Elizabeth C. Coronel, John N. FainAbstract:Peroxovanadate (PVN) is an insulin-like agent that inhibits the dephosphorylation of the insulin Receptor kinase. PVN inhibited the lipolytic action of 0.1 microM isoproterenol by 88%, which is a relatively specific beta 1 catecholamine agonist at this concentration, but was largely ineffective against beta 3 agonists or forskolin. To determine whether PVN-mediated desensitization of the beta 1 AR was associated with enhanced phosphorylation, we immunoprecipitated the beta 1 AR from rat adipocytes that were metabolically labeled with 32PO4. Isoproterenol enhanced the net phosphorylation of the beta 1 AR by 8 +/- 2-fold over control. PVN increased the net phosphorylation of the beta 1 AR by 5 +/- 0.5-fold, and together with isoproterenol, they enhanced the phosphorylation of the beta 1 AR by 2-fold over isoproterenol alone. Phosphoamino acid analysis of the phosphorylated Receptor revealed phosphate incorporation into serine that was proportional to the radioactivity incorporated into the immunoprecipitated Receptor. PVN inhibited the serine/threonine phosphatase calcineurin, suggesting that inhibition of Receptor dephosphorylation may play a role in the actions of PVN. Cyanogen bromide cleavage of the phosphorylated beta 1 AR generated a phosphoprotein with a molecular mass consistent with carboxyl-terminal phosphorylation. Furthermore, the magnitude of Receptor phosphorylation by isoproterenol was 3-fold larger than that due to forskolin, suggesting that beta 1 AR is a substrate for the beta AR kinase that phosphorylates carboxyl-terminal residues in the beta(2) AR. Our findings suggest that PVN may be a powerful new tool with which to study the phosphorylation of other G protein-coupled Receptors.
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Glucocorticoids down-regulate β1-Adrenergic-Receptor expression by suppressing transcription of the Receptor gene
Biochemical Journal, 1994Co-Authors: J Kiely, Suleiman W. Bahouth, J R Hadcock, Craig C. MalbonAbstract:The expression of beta 2-Adrenergic Receptors is up-regulated by glucocorticoids. In contrast, beta 1-Adrenergic Receptors display glucocorticoid-induced down-regulation. In rat C6 glioma cells, which express both of these subtypes of beta-Adrenergic Receptors, the synthetic glucocorticoid dexamethasone stimulates no change in the total beta-Adrenergic Receptor content, but rather shifts the beta 1:beta 2 ratio from 80:20 to 50:50. Radioligand binding and immunoblotting demonstrate a sharp decline in beta 1-Adrenergic Receptor expression. Metabolic labelling of cells with [35S]-methionine in tandem with immunoprecipitation by beta 1-Adrenergic-Receptor-specific antibodies reveals a sharp decline in the synthesis of the Receptor within 48 h for cells challenged with glucocorticoid. Steady-state levels of beta 1-Adrenergic-Receptor mRNA declined from 0.47 to 0.26 amol/microgram of total cellular RNA within 2 h of dexamethasone challenge, as measured by DNA-excess solution hybridization. The stability of Receptor mRNA was not influenced by glucocorticoid; the half-lives of the beta 1- and beta 2-subtype mRNAs were 1.7 and 1.5 h respectively. Nuclear run-on assays revealed the basis for the down-regulation of Receptor expression, i.e. a sharp decline in the relative rate of transcription for the beta 1-Adrenergic-Receptor gene in nuclei from dexamethasone-treated as compared with vehicle-treated cells. These data demonstrate transcriptional suppression as a molecular explanation for glucocorticoid-induced down-regulation of beta 1-Adrenergic Receptors.
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Effects of chemical and surgical sympathectomy on expression of beta-Adrenergic Receptors and guanine nucleotide-binding proteins in rat submandibular glands.
Molecular pharmacology, 1992Co-Authors: Suleiman W. BahouthAbstract:Expression of beta 1-Adrenergic Receptors and guanine nucleotide-binding proteins in rat submandibular glands was determined after reserpine administration and sympathetic denervation. Pretreatment of rats with reserpine resulted in up-regulation of the density of beta 1-Adrenergic Receptors and the immunoreactivity of the 64-kDa species of beta 1-Adrenergic Receptor in submandibular membranes, by 2.6 +/- 0.3-fold (eight experiments), within 7 days. Steady state levels of beta 1-Adrenergic Receptor mRNA quantified by DNA-excess solution hybridization were 0.15 +/- 0.03 amol of beta 1-Adrenergic Receptor mRNA/micrograms of total cellular RNA (six experiments). beta 1-Adrenergic Receptor mRNA increased by 50% within 8 hr after pretreatment with reserpine. Maximal levels of 0.37 +/- 0.04 amol of beta 1-Adrenergic Receptor mRNA/micrograms of RNA were attained by 4 days and these levels were sustained for the next 3 days (six experiments). Northern blot hybridization also revealed a 3-fold increase in the 2.5-kilobase beta 1-Adrenergic Receptor mRNA transcript, which was equivalent in magnitude to that determined by solution hybridization. Reserpine pretreatment also affected steady state levels of submandibular guanine nucleotide-binding proteins. Two immunoreactive forms of the alpha subunit of Gs, migrating as 42 kDa (major) and 50 kDa (minor), were detected in salivary membranes. The immunoreactivity of the 42-kDa species of Gs alpha declined by 50% after 7 days of continuous daily injections of reserpine. In contrast, steady state levels of Gi alpha 2 (41 kDa), Go (39 kDa), and G beta 2 (35 kDa) and their mRNAs in submandibular membranes were unaffected by reserpine pretreatment. The rate of beta 1-Adrenergic Receptor gene transcription assessed by nuclear run-on transcription assay in nuclei of submandibular glands was not altered by reserpine pretreatment. However, reserpine had a dramatic effect on the half-life of beta 1-Adrenergic Receptor mRNA in submandibular glands. The half-life of beta 1-Adrenergic Receptor mRNA in control submandibular glands was 3.5 hr, whereas it increased to 8 hr in reserpine-pretreated glands. Reserpine-promoted stabilization of beta 1-Adrenergic Receptor mRNA provides a mechanism for up-regulation of postjunctional beta 1-Adrenergic Receptors in sympathetically innervated tissues.