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Results for “Receptors, Adrenergic”

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At least 19 recordsLinked to original sources
PubMed2003

UV cross-linking/immunoprecipitation assay: glucocorticoid receptor-adrenergic receptor gene sequence interaction.

The rat beta 1-adrenergic receptor (beta 1-AR) gene contains glucocorticoid response element (GRE) half-sites at positions -2767 and -945. In electrophoretic mobility shift assay (EMSA) experiments, neither beta 1-AR GRE half-site recognized glucocorticoid receptors (GRs) obtained from baculovirus high-level expression systems or from mammalian cells. We have developed a sensitive UV cross-linking/immunoprecipitation assay, using a 524-bp fragment containing the prototypical GRE obtained from the rat tyrosine aminotransferase promoter sequence and using antibodies recognizing mammalian GR. Using this assay, we provide evidence that rat beta 1-AR gene sequences recognize mammalian GRs expressed in mouse 3T3 cells and that the site of GR interaction does not appear to specifically contain the beta 1-AR GRE half-sites. This represents one of the first reports demonstrating the utility of a UV cross-linking/immunoprecipitation assay in the detection of mammalian GR interaction with beta 1-AR sequences, is consistent with the lack of specific DNA-GR protein complexes observed in EMSA experiments using oligonucleotide probes containing the beta 1-AR GRE half-sites, and provides evidence that mammalian GR interaction occurs at complex rate beta 1-AR gene sequences.

3T3 Cells↗
PubMed1992

Identification of intramolecular interactions in adrenergic receptors.

Adrenergic receptors are representative of a large family of plasma membrane receptors that interact with G proteins during the process of transmembrane signal transduction. G protein-coupled receptors have a primary structure that is homologous to bacteriorhodopsin and are proposed to have a similar three-dimensional structure; however, it has not yet been possible to examine this hypothesis experimentally. We have used a novel mutagenesis approach to identify intramolecular interactions. Our results indicate that specific amino acids in the seventh hydrophobic segment of alpha 2 and beta 2 adrenergic receptors lie adjacent to the first hydrophobic segment. These studies provide the first experimental evidence defining spatial relationships that exist in the three-dimensional structure of adrenergic receptors.

Humans↗
PubMed1982

Adrenergic influence on iris stromal pigmentation: evidence for alpha-adrenergic receptors.

Adrenergic influence on iris pigmentation in newborn pigmented rabbits was studied. Selective adrenergic antagonists were used topically to determine whether they could inhibit iris pigmentation. Unilateral, topical administration of an alpha-adrenergic antagonist (thymoxamine hydrochloride 1/2%) was not associated with iris hypochromia. Adrenergic influence on iris stromal melanogenesis appears to be mediated by alpha-adrenergic receptors.

Animals↗
PubMed1980

Activation of lateral geniculate neurons by norepinephrine: mediation by an alpha-adrenergic receptor.

Adrenergic receptors in the vicinity of neurons in the lateral geniculate nucleus (LGN) of the rat were pharmacologically characterized using extracellular single-cell recording and microiontophoretic techniques. Application of norepinephrine (NE) at low iontophoretic currents (1-15 nA) produced a delayed activation of most LGN neurons. This activation was mimicked by various sympathomimetic amines. The relative potency series of agonists was typical of postsynaptic alpha-adrenergic receptors: epinephrine greater than NE greater than phenylephrine greater than or equal to alpha-methylnorepinephrine greater than dopamine greater than isoproterenol. The alpha-antagonists phentolamine, piperoxane and WB-4101, when applied at low iontophoretic currents (less than 10 nA), produced a selective, dose-dependent and reversible blockade of the response to NE. The beta-antagonist sotalol had weak and variable effects at these currents. At low currents, the presynaptic alpha-agonist clonidine was also able to block the response to NE but, at higher currents, produced a partial activation of some units, suggesting that it is a weak agonist. The ability of sympathomimetic amines to activate LGN neurons correlates well with their reported affinities for brain alpha1-adrenoceptors labeled with [3H]WB-4101. It is concluded that NE activates neurons in the LGN via a postsynaptic or alpha1-adrenergic receptor.

Adrenergic alpha-Antagonists↗
PubMed1993

Structure, function, and regulation of adrenergic receptors.

Adrenergic receptors for adrenaline and noradrenaline belong to the large multigenic family of receptors coupled to GTP-binding proteins. Three pharmacologic types have been identified: alpha 1-, alpha 2-, and beta-adrenergic receptors. Each of these has three subtypes, characterized by both structural and functional differences. The alpha 2 and beta receptors are coupled negatively and positively, respectively, to adenylyl cyclase via Gi or Gs regulatory proteins, and the alpha 1 receptors modulate phospholipase C via the Go protein. Subtype expression is regulated at the level of the gene, the mRNA, and the protein through various transcriptional and postsynthetic mechanisms. Adrenergic receptors constitute, after rhodopsin, one of the best studied models for the other receptors coupled to G proteins that are likely to display similar structural and functional properties.

Amino Acid Sequence↗
PubMed1990

Comorbidity of panic disorder and major depressive disorder: effects on platelet alpha 2 adrenergic receptors.

Adrenergic receptor dysregulation has been described as occurring in both major depressive disorder (MDD) and panic disorder. Measurements of platelet alpha 2 adrenergic receptors in these patients may be confounded by the coexistence or comorbidity of both diagnoses in the same patient. To explore this possibility, we measured platelet alpha 2 adrenergic receptors (3H-clonidine and 3H-yohimbine binding) in 3 groups of patients (MDD only, panic disorder only, and those showing comorbidity of MDD and panic) and normal controls. Patients with comorbidity of MDD and panic disorder had significantly lower agonist binding (3H-clonidine).

Adult↗
PubMedDate not supplied

Patterns of adrenergic receptors and adrenergic agonists underlying cardiovascular responses to a psychological challenge.

Numerous physiological and biochemical factors contribute to the dynamic regulation of the cardiovascular system. This study used a cluster analytic statistical technique to discern patterns of adrenergic receptors and adrenergic agonists underlying cardiovascular responses to a laboratory challenge. Fifty hypertensive and normotensive black and white individuals had their beta- and alpha-adrenergic receptor sensitivity determined through agonist infusions. Norepinephrine, epinephrine, blood pressure, and heart rate responses to a standardized mental arithmetic task were also obtained. The cluster analysis identified four subgroups of individuals having distinct patterns of receptor and neurohormonal regulation of end-organ responses. In general, the data indicated that end-organ cardiovascular responses are, in part determined by the sensitivity of adrenergic receptors and the accompanying catecholamine responses. The findings also suggest that for some individuals nonadrenergic factors play a more dominant role than adrenergic mechanisms in determining cardiovascular pressor responses.

Adult↗
PubMed1986

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

The involvement of postsynaptic alpha 2-adrenergic receptors in the adrenergic constriction of the capacitance vessels was studied in anesthetized, spontaneously breathing dogs under ganglionic blockade (hexamethonium, 10 mg/kg + 10 mg/kg/hr; methylatropine, 0.5 mg/kg). Effective vascular compliance was measured as an indicator of venous tone (blood volume was varied by +/- 4 ml/kg in an 11-minute cycle of infusion, withdrawal, withdrawal, and reinfusion) and was calculated from the correlation between the observed changes in central venous pressure and the changes in blood volume. Sympathetic activity and central venous pressure were lower and effective vascular compliance was higher than values in untreated conscious dogs. The alpha 2-agonist UK 14,304 (5-bromo-6-[imidazolin-2-ylamino]-quinoxaline; 0.04 and 0.12 micrograms/kg/min; n = 6) dose-dependently lowered compliance and increased central venous pressure to levels found in conscious dogs, as did the alpha 1-agonist methoxamine (10 and 30 micrograms/kg; n = 6). Rauwolscine (alpha 2-antagonist), 0.3 mg/kg, significantly attenuated the effects of UK 14,304, but not those of methoxamine, while prazosin (alpha 1-antagonist), 0.12 mg/kg, attenuated the effects of methoxamine, but not those of UK 14,304 (n = 6 each). Under beta-blockade (nadolol, 2 mg/kg; n = 12) venous tone was increased to about physiological levels by norepinephrine, 0.15 micrograms/kg/min i.v., or by neuronal norepinephrine release induced by tyramine, 10 micrograms/kg/min i.v. These increases were significantly attenuated by prazosin as well as by rauwolscine and were abolished by a combination of both. These results indicate that postsynaptic alpha 2-adrenergic receptors (in addition to alpha 1-adrenergic receptors) are functional in the venous system in vivo and contribute substantially to adrenergic sympathetic and humoral regulation of venous tone.

Adrenergic alpha-Antagonists↗
PubMed1983

Roles of alpha 1- and beta-adrenergic receptors in adrenergic responsiveness of liver cells formed after partial hepatectomy.

The adrenergic receptor involved in the action of epinephrine changed dramatically during the process of active proliferation which follows partial hepatectomy. In control or sham-operated animals, the stimulation of glycogenolysis, gluconeogenesis and ureogenesis by epinephrine was mediated through alpha 1-adrenergic receptors. In contrast, in hepatocytes obtained from animals partially hepatectomized 3 days before experimentation, the receptor involved in the stimulation of these metabolic pathways by epinephrine was of the beta-adrenergic type. Interestingly, the adrenergic receptor involved in the metabolic actions of epinephrine, in hepatocytes from rats partially hepatectomized 7 days before experimentation was again of the alpha 1-subtype. Thus, it appears that during the process of liver regeneration which follows partial hepatectomy there is a transition in the type of adrenergic receptor involved in the hepatic actions of catecholamines from beta in the initial stages to later alpha 1. A similar transition seems to occur as the animal ages. Cyclic AMP accumulation in response to beta-adrenergic stimulation was significantly enhanced in hepatocytes obtained from rats partially hepatectomized 3 days before the experiment, as compared to control hepatocytes or cells obtained from animals operated 7 days before experimentation. This enhanced beta-adrenergic sensitivity is probably related to the increased number of beta-adrenergic receptors observed at this stage. However, a clear dissociation between cyclic AMP levels and metabolic effects was evidenced when the different conditions were compared. The number and affinity (for epinephrine or prazosin) of alpha 1-adrenergic receptors did not change at any stage of the process, which indicates that the markedly diminished alpha 1-adrenergic sensitivity observed in hepatocytes obtained from rats partially hepatectomized 3 days before experimentation is probably due to defective generation or intracellular processing of the alpha 1-adrenergic signal, rather than to changes at the receptor level.

Animals↗
PubMed2003

Functional interactions between mu opioid and alpha 2A-adrenergic receptors.

Adrenergic and opioid receptors belong to the rhodopsin family of G-protein coupled receptors, couple to analogous signal transduction pathways, and affect the nociceptive system. Although a number of previous studies have reported functional interactions between these two receptors, the basis for this has not been well explored. We propose that direct receptor-receptor interactions could account, in part, for opioid-adrenergic cross-talk. In this report, we have addressed this using biophysical, biochemical, and pharmacological studies. We show that mu opioid and alpha2A adrenergic receptors reside in close proximity in live cells using the bioluminescence resonance energy transfer assay. These receptors colocalize to proximal dendrites in primary hippocampal neurons. mu-alpha2A Receptor complexes can be isolated from heterologous cells or primary neurons coexpressing these receptors. In these cells, the activation of either mu or alpha2A receptor leads to a significant increase in the level of immunoprecipitable mu-alpha2A complexes, whereas activation of both receptors leads to a significant decrease. The implications of these effects on signaling were examined using the agonist-mediated increase in G-protein activity and mitogen-activated protein kinase activity. We find that activation of either mu or alpha2A receptors leads to an increase in the extent of signaling, whereas activation of both receptors leads to a decrease. The increase in signaling by individual ligands and decrease by a combination of ligands is also seen in primary spinal cord neurons endogenously expressing these receptors. Taken together, these results suggest that physical associations between mu and alpha2A receptors could play a role in the functional interactions between these receptors.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1994

The modelling of beta 2-adrenergic receptors.

Adrenergic mimetics have many varied pharmacological applications, thus the quest for selective and efficacious ligands. Provided that a reasonable receptor model can be constructed which mimics the key interactions between a ligand and its biological receptor, molecular modelling offers the potential for rational drug design. The beta 2-adrenergic receptor models reviewed in this article have increased in sophistication, in line with more information becoming available about the residues involved in ligand binding, as well as the topography of the receptor.

Animals↗
PubMed1991

Cross-regulation between G-protein-coupled receptors. Activation of beta 2-adrenergic receptors increases alpha 1-adrenergic receptor mRNA levels.

Stimulation of DDT1 MF-2 vas deferens cells with epinephrine resulted in a time- and dose-dependent loss of alpha 1-adrenergic receptor-specific ligand binding. Regulation of alpha 1-adrenergic receptor mRNA was characterized. In monolayer culture, cells displayed 0.7 +/- 0.05 amol of alpha 1-adrenergic receptor mRNA/microgram of total cellular RNA. Epinephrine, which acts at both alpha 1- and beta 2-adrenergic receptors of DDT1 MF-2 cells, induced a short term (2-8 h) increase (50-70%) in the abundance of alpha 1-adrenergic receptor mRNA. Propranolol, a beta 2-adrenergic receptor antagonist, attenuated the epinephrine-mediated increase in alpha 1-adrenergic receptor mRNA but did not affect the decrease in alpha 1-adrenergic receptor-specific ligand binding. Phentolamine, an alpha 1-adrenergic receptor antagonist, did not attenuate the epinephrine-mediated increase in alpha 1-adrenergic receptor mRNA at 4 h but did block the decrease in alpha 1-adrenergic receptor-specific ligand binding. The half-life of the alpha 1-adrenergic receptor mRNA was approximately 7 h in untreated cells as well as in cells challenged with epinephrine. The epinephrine-promoted increase in alpha 1-adrenergic receptor mRNA was found to result from cross-regulation via beta 2-adrenergic receptors. Cholera toxin, forskolin, as well as the cyclic AMP analog CPT cAMP (8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate) increased the alpha 1-adrenergic receptor mRNA at 4 h, as did epinephrine in the presence of alpha 1-antagonists but not in the presence of a beta-adrenergic antagonist. This is the first report of heterologous up-regulation of mRNA levels of adrenergic receptors. Cross-regulation between alpha 1- and beta 2-adrenergic receptor-mediated pathways at 4 h occurs at the level of mRNA whereas later down-regulation of alpha 1-receptor mRNA and binding proceed via agonist activation of alpha 1-adrenergic receptors.

Animals↗
PubMed2003

Downstream coding region determinants of bacterio-opsin, muscarinic acetylcholine receptor and adrenergic receptor expression in Halobacterium salinarum.

The aim of this work is to develop a prokaryotic system capable of expressing membrane-bound receptors in quantities suitable for biochemical and biophysical studies. Our strategy exploits the endogenous high-level expression of the membrane protein bacteriorhodopsin (BR) in the Archaeon Halobacterium salinarum. We attempted to express the human muscarinic acetylcholine (M(1)) and adrenergic (a2b) receptors by fusing the coding region of the m1 and a2b genes to nucleotide sequences known to direct bacterio-opsin (bop) gene transcription. The fusions included downstream modifications to produce non-native carboxyl-terminal amino acids useful for protein identification and purification. bop mRNA and BR accumulation were found to be tightly coupled and the carboxyl-terminal coding region modifications perturbed both. m1 and a2b mRNA levels were low, and accumulation was sensitive to both the extent of the bop gene fusion and the specific carboxyl-terminal coding sequence modifications included. Functional a2b adrenergic receptor expression was observed to be dependent on the downstream coding region. This work demonstrates that a critical determinant of expression resides in the downstream coding region of the wild-type bop gene and manipulation of the downstream coding region of heterologous genes may affect their potential for expression in H. salinarum.

Amino Acid Sequence↗
PubMed1997

A critical period for the role of thyroid hormone in development of renal alpha-adrenergic receptors.

Adrenergic input influences renal cell replication/differentiation and the development of excretory function. Kidney cells make adrenoceptors before the arrival of the majority of nerve terminals, and the current study examines whether thyroid hormone plays a role in receptor development. Propylthiouracil (PTU) was given to pregnant and neonatal rats from gestational d 17 through postnatal d 5, a treatment that obtunds thyroid hormone levels throughout the first 2-3 wk postpartum. The PTU group showed significant deficits in the number of alpha1-receptors, and values resolved to normal in parallel with hormone level recovery. The effects were not secondary to alterations in cell differentiation or growth. as the period of receptor abnormalities did not correspond to that of growth inhibition. Similarly, the effects were selective for the alpha1-receptor, as no comparable effects were seen for total membrane protein or for alpha2-receptors. The role of thyroid hormone in alpha1-receptor ontogeny involved a critical developmental window; later in development neither treatment with PTU nor with large doses of thyroid hormone had any impact on alpha1-receptors. Studies of mRNAs encoding the alpha1-receptor subtypes indicated that hypothyroidism targets the alpha1a-subtype, which has been implicated in the transduction of neurotrophic signals; alpha1a-receptor mRNA also showed the largest proportional developmental increase compared with those encoding other alpha1-subtypes. Accordingly, thyroid hormone is likely to set the stage for the subsequent trophic control of renal development by neural input, and hypothyroidism during this critical window can be expected to result in abnormal renal functional development and increased perinatal risk.

Animals↗
PubMed1993

Absence of functional inhibition of cloned human beta 2-adrenergic receptors by autoantibodies in asthmatic subjects.

Using guinea-pig lung membranes and cloned human beta 2-receptor adrenergic receptors the effects of whole serum, plasma, purified immunoglobulins and cellular activation products on beta 2-adrenergic receptor ligand binding and function were investigated. Sera from 24 non-asthmatic subjects and 115 asthmatics in different clinical categories were studied. There were no significant differences between antagonist ([125I] cyanopindolol) inhibition mediated by serum, plasma or by purified IgG when the asthmatics were compared with non-asthmatics. There was also no inhibition of 10(-6) M isoproterenol stimulated cAMP release from L cells expressing human beta 2-adrenergic receptors, by plasma, DEAE purified IgG fractions from asthmatics and non-asthmatics, or by products of activated platelets or lymphocytes. Since we have no evidence that immunoglobulins from asthmatic subjects exert functional inhibition of human beta 2-adrenergic receptors we conclude that autoantibodies to the beta 2-adrenergic receptors do not play an important functional role in the pathophysiology of asthma.

Adrenergic beta-Agonists↗
PubMed1987

Agonist-dependent phosphorylation of the alpha 2-adrenergic receptor by the beta-adrenergic receptor kinase.

Desensitization of the beta-adrenergic receptor, a receptor which is coupled to the stimulation of adenylate cyclase, may be regulated via phosphorylation by a unique protein kinase. This recently discovered enzyme, known as the beta-adrenergic receptor kinase, only phosphorylates the agonist-occupied form of the beta-adrenergic receptor. To assess whether receptors coupled to the inhibition of adenylate cyclase might also be substrates, we examined the effects of beta-adrenergic receptor kinase on the partially purified human platelet alpha 2-adrenergic receptor. Phosphorylation of the reconstituted alpha 2-adrenergic receptor was dependent on agonist occupancy and was completely blocked by coincubation with alpha 2-antagonists. The time course of phosphorylation of the alpha 2-adrenergic receptor was virtually identical to that observed with the beta-adrenergic receptor with maximum stoichiometries of 7-8 mol of phosphate/mol of receptor in each case. In contrast, the alpha 1-adrenergic receptor, which is coupled to stimulation of phosphatidylinositol hydrolysis, is not a substrate for the beta-adrenergic receptor kinase. These results suggest that receptors coupled to either stimulation or inhibition of adenylate cyclase may be regulated by an agonist-dependent phosphorylation mediated by the beta-adrenergic receptor kinase.

Affinity Labels↗
PubMed1998

Relaxation of isolated human myometrial muscle by beta2-adrenergic receptors but not beta1-adrenergic receptors.

OBJECTIVE: Human myometrium contains both beta1-adrenergic and beta2-adrenergic receptors. This study was designed to assess the importance of each beta-adrenergic receptor subtype in relaxation of human myometrial muscle strips. STUDY DESIGN: Radioligand binding studies were used to establish the presence of each beta-adrenergic receptor subtype, whereas highly selective beta1-antagonists and beta2-antagonists were used to assess the contribution of beta-adrenergic receptor subtypes to myometrial relaxation after exposure to (-)-isoproterenol. RESULTS: Membranes prepared from myometrium contained 82% +/- 4% beta2-adrenergic receptors. After contraction produced by exposure to potassium chloride (35 mmol/L), isoproterenol produced relaxation with half maximal effect at 0.02 micromol/L and a maximal relaxation of 52% +/- 3%. Beta1-antagonist CGP-20712A had no significant effect, whereas beta2-antagonist ICI-118551 produced a characteristic rightward shift of the isoproterenol concentration-relaxation relationship. CONCLUSIONS: Although both beta1-adrenergic receptors and beta2-adrenergic receptors are present in human myometrial tissue at term, relaxation by nonselective beta-agonist isoproterenol is mediated exclusively by beta2-adrenergic receptors.

Adrenergic beta-Agonists↗