Gα I3 Research Articles

Differential ligand efficacy at h5-HT 1A receptor-coupled G-protein subtypes: a commentary

Activation of heterotrimeric G-protein involves the exchange by α subunits of GDP for GTP. The binding of the hydrolysis-resistant GTP analogue, guanosine-5′- O-(3-[ 35S]thio)-triphosphate ([ 35S]GTPγS), provides a measure of agonist, antagonist and inverse agonist actions at G-protein-coupled receptors. However, classical [ 35S]GTPγS binding methods do not distinguish among the subtypes of G-proteins activated. This is a limitation in view of (i) promiscuity of receptor coupling to multiple families of G-proteins, and (ii) the differential influence of ligands on distinct signal transduction pathways. A recent development of [ 35S]GTPγS binding methodology employing antibody capture and scintillation proximity assays (SPA) permits the targeting of specific Gα subtypes in both recombinant and native tissues. When applied to human serotonin 1A receptor (h5-HT 1A) expressed in Chinese hamster ovary (CHO) cells, this methodology revealed surprising patterns of Gα i3 subunit activation. For example, low but not high concentrations of high-efficacy h5-HT 1A agonists direct receptor signalling to Gα i3. In contrast, partial agonists favour h5-HT 1A receptor signalling to Gα i3 over a wide concentration range. Further, alterations in buffer sodium concentration reversed these actions of agonists: stimulation of Gα i3 activation was observed at high sodium concentration, but inhibition was observed at low sodium concentration, suggestive of protean efficacy, i.e. a switch from positive to negative efficacy dependent on receptor tone. These results indicate that complex changes in both magnitude and direction of response to receptor ligands can occur for specific G-protein subtypes. Interestingly, the inverse agonist, spiperone, inhibited constitutive h5-HT 1A receptor-mediated Gα i3 activation under all conditions tested, consistent with the hypothesis that it selectively stabilises distinct receptor conformation(s). Further, whereas classical [ 35S]GTPγS binding assays in CHO cell membranes failed to demonstrate negative efficacy for the neuroleptic, haloperidol, this compound exhibited robust inverse agonism for the activation of Gα i3 subunits. These data suggest that haloperidol may selectively inhibit constitutive activation of this G-protein subtype and, thus, exhibit inverse agonist-mediated trafficking of receptor signalling.

Albumin: a Gα s-specific guanine nucleotide dissociation inhibitor and GTPase activating protein

Heterotrimeric GTP binding protein (G protein)-mediated signal transduction events are regulated by their effectors and regulators of G protein signaling (RGS) protein family. The latter proteins function as GTPase activating proteins (GAPs) for G protein α subunits and terminate signaling events. In a search for proteins that modulate the activity of the stimulatory G protein of adenylyl cyclase (Gα s), we found that bovine serum albumin (BSA) inhibits the steady-state GTPase activity of Gα s, but not the inhibitory G protein (Gα i1). This effect of BSA is mediated by decreasing the rate of GDP dissociation from Gα s and decreasing the rate of GTP binding. Thus, BSA functions as a guanine nucleotide dissociation inhibitor for Gα s. Moreover, BSA also increased the intrinsic GTPase activity of Gα s, but not Gα i1, demonstrating that BSA functions as a Gα s-specific GAP. Using mutants of Gα s (Q227L, Q227N, R201C, and R201K), we demonstrate that BSA mediates its GAP function by modulating the ability of R201 to increase GTPase activity. Moreover, using wild-type and Q227N forms of Gα s, our studies demonstrate that the GDI function of BSA decreases the ability of Gα s to stimulate adenylyl cyclase. These findings assign a novel function to BSA as a regulator of G protein signaling.

Sphingosylphosphorylcholine-induced contraction of feline ileal smooth muscle cells is mediated by Gα i3 protein and MAPK

We studied the mechanism of sphingosylphosphorylcholine (SPC)-induced contraction in feline ileal smooth muscle cells. Western blotting revealed that G protein subtypes of Gα i1, Gα i3 and Gα o existed in feline ileum. Gα i3 antibody penetration into permeabilized cells decreased SPC-induced contraction. In addition, incubation of [ 35S]guanosine 5′- O-(3-thiotriphosphate) ([ 35S]GTPγS) with membrane fraction increased its binding to Gα i3 subtype after SPC treatment, suggesting that the signalling pathways invoked by SPC were mediated by Gα i3 protein. MAPK kinase (MEK) inhibitor PD98059 blocked the contraction significantly, but p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 did not. Chelerythrine and neomycin also inhibited the contraction. However, cotreatment of PD98059 and chelerythrine showed no significant difference. Phosphorylation of p44/42 MAPK was increased by SPC treatment, which was reversed by pretreatment of inhibitors of signalling molecules that decreased SPC-induced contraction previously. The same result was obtained in the assay of MAPK activity.

C-Terminal exchange between Gα o and Gα i3 proteins differently modulates α2A-adrenoceptor activation

Chimeric Gα proteins, obtained by exchanging their C-terminal portion for that of a Gα protein from an unrelated class, drive the receptor selectivity to that corresponding to the introduced Gα protein domain. The α2A-adrenoceptor (α2AAR), which yielded an efficacious and weak [35S]GTPγS binding response by respectively Gα o and Gα i3 protein, was investigated in CHO-K1 cells co-expressing chimeric Gα proteins for which the six last C-terminal amino acids between Gα o and Gα i3 proteins, and reciprocally, were permuted. Activation of the chimeric Gα o / i3 protein was highly efficient whereas the Gα i3 / o protein yielded a weak stimulation. These [35S]GTPγS binding responses were not different from their parental wild-type Gα o and Gα i3 proteins. Similar results were obtained with an α2AAR carrying a facilitating Thr373Lys mutation in a putative G protein interaction domain. These data indicate that the six terminal Gα o protein amino acids do not constitute a major α2AAR interaction domain for Gα protein activation.

Gα i Controls the Gating of the G Protein-Activated K + Channel, GIRK

GIRK (Kir3) channels are activated by neurotransmitters coupled to G proteins, via a direct binding of G βγ. The role of Gα subunits in GIRK gating is elusive. Here we demonstrate that Gα i is not only a donor of Gβγ but also regulates GIRK gating. When overexpressed in Xenopus oocytes, GIRK channels show excessive basal activity and poor activation by agonist or Gβγ. Coexpression of Gα i3 or Gα i1 restores the correct gating parameters. Gα i acts neither as a pure Gβγ scavenger nor as an allosteric cofactor for Gβγ. It inhibits only the basal activity without interfering with Gβγ-induced response. Thus, GIRK is regulated, in distinct ways, by both arms of the G protein. Gα i probably acts in its GDP bound form, alone or as a part of Gαβγ heterotrimer.

Possible involvement of G i3 protein in augmented contraction of bronchial smooth muscle from antigen-induced airway hyperresponsive rats

To investigate a possible involvement of pertussis toxin (PTX)-sensitive heterotrimeric G proteins in the pathogenesis of airway hyperresponsiveness, the effect of PTX treatment on the augmented contractile response to acetylcholine (ACh) in bronchial smooth muscle of antigen-induced airway hyperresponsive rats was determined. In bronchial smooth muscle of airway hyperresponsive rats that were actively sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen, ACh-induced contractions were markedly augmented. The augmented contractile responses in the airway hyperresponsive group were significantly inhibited after treatment with PTX (1 μg/mL for 6 hr, 37°), whereas only a slight attenuation was observed in the normal control group. The level of Gα i3 (measured by immunoblotting), but not other α-subunits of G i/o family proteins, in bronchial smooth muscle of the airway hyperresponsive rats was significantly increased as compared with that of control animals. It is concluded that PTX-sensitive muscarinic contractile responses of bronchial smooth muscle might be augmented upon antigen-induced airway hyperresponsiveness in rats, probably due to an up-regulation of Gα i3 protein of bronchial smooth muscle.

Characterization of RGS5 in regulation of G protein-coupled receptor signaling

RGS proteins (regulators of G protein signaling) serve as GTPase-activating proteins (GAPs) for Gα subunits and negatively regulate G protein-coupled receptor signaling. In this study, we characterized biochemical properties of RGS5 and its N terminal (1-33)-deleted mutant (ΔN-RGS5). RGS5 bound to Gα i1, Gα i2, Gα i3, Gα o and Gα q but not to Gα s and Gα 13 in the presence of GDP/AlF 4 −, and accelerated the catalytic rate of GTP hydrolysis of Gα i3 subunit. When expressed in 293T cells stably expressing angiotensin (Ang) AT 1a receptors (AT 1a-293T cells), RGS5 suppressed Ang II- and endothelin (ET)-1-induced intracellular Ca 2+ transients. The effect of RGS5 was concentration-dependent, and the slope of the concentration-response relationship showed that a 10-fold increase in amounts of RGS5 induced about 20–25 % reduction of the Ca 2+ signaling. Furthermore, a comparison study of three sets of 293T cells with different expression levels of AT 1a receptors showed that RGS5 inhibited Ang II-induced responses more effectively in 293T cells with the lower density of AT 1a receptors, suggesting that the degree of inhibition by RGS proteins reflects the ratio of amounts of RGS proteins to those of activated Gα subunits after receptor stimulation by agonists. When expressed in AT 1a-293T cells, ΔN-RGS5 was localized almost exclusively in the cytosolic fraction, and exerted the inhibitory effects as potently as RGS5 which was present in both membrane and cytosolic fractions. Studies on relationship between subcellular localization and inhibitory effects of RGS5 and ΔN-RGS5 revealed that the N terminal (1-33) of RGS5 plays a role in targeting this protein to membranes, and that the N terminal region of RGS5 is not essential for exerting activities.

Opioid-induced adenylyl cyclase supersensitization in human embryonic kidney 293 cells requires pertussis toxin-sensitive G proteins other than G i1 and G i3

Chronic activation of opioid receptors in cultured mammalian cells is known to induce adenylyl cyclase (AC) supersensitization via the pertussis toxin-sensitive G i/o proteins. To examine the role of G i1 and G i3 in opioid-induced AC supersensitization, pertussis toxin-resistant mutants of Gα i1 and Gα i3 (Gα i1CG and Gα i3CG) were stably co-expressed with different opioid receptors (μ, δ or κ) in human embryonic kidney (HEK 293) cells. Although the opioid receptors were capable of inhibiting AC via Gα i1CG and Gα i3CG in pertussis toxin-treated cells, AC supersensitization induced by chronic opioid treatment remained sensitive to pertussis toxin. Our results demonstrated that despite their ability to interact with opioid receptors, the pertussis toxin-sensitive G i1 and G i3 proteins on their own are incapable of supporting opioid-induced AC supersensitization.

Modulation of adenylyl cyclase by FPP and adenosine involves stimulatory and inhibitory adenosine receptors and g proteins.

FPP and adenosine modulate the adenylyl cyclase (AC)/cAMP signal transduction pathway in mammalian spermatozoa to elicit a biphasic response, initially stimulating capacitation and then inhibiting spontaneous acrosome loss. This study addressed the hypothesis that responses to FPP involve interactions between receptors for FPP and adenosine, the biphasic responses involving stimulatory and inhibitory adenosine receptors. Gln-FPP, a competitive inhibitor of FPP, significantly inhibited binding of an adenosine analogue and responses to adenosine, especially in capacitated suspensions, consistent with interaction between FPP and adenosine receptors. CGS-21680 (1 microM), a stimulatory A2a adenosine receptor agonist, significantly stimulated capacitation and cAMP in uncapacitated cells, while cyclopentyl adenosine (1 microM), an inhibitory A1 adenosine receptor agonist only affected capacitated cells, inhibiting spontaneous acrosome loss. Responses to FPP and adenosine were inhibited in uncapacitated cells by a selective A2a antagonist and in capacitated cells by a selective A1 antagonist; subsequent investigations indicated possible involvement of G proteins. Like FPP, cholera toxin stimulated capacitation and cAMP production in uncapacitated cells, suggesting involvement of a G protein with a Galphas subunit. In contrast, pertussis toxin prevented FPP's inhibition of both spontaneous acrosome loss and cAMP production, suggesting involvement of a Galphai/o subunit. Immunoblotting evidence revealed the presence of proteins of the appropriate molecular weights for Galphas, Galphai2, Galpha i3, and Galphao subunits. This study provides the first direct evidence suggesting the involvement of two different types of adenosine receptors and both Galphas and Galphai/o subunits in the regulation of capacitation, resulting in modulation of AC activity and availability of cAMP.

Leukotriene D 4 induces a rapid increase in cAMP in the human epithelial cell line, Int 407: a potential role for this signal in the regulation of calcium influx through the plasma membrane

Although the LTD 4-induced Ca 2+ influx in human epithelial cells has been shown to be regulated by a pertussis toxin-sensitive heterotrimeric G-protein, most likely a Gα i3 protein [Adolfsson J.L.P., Öhd J.F., Sjölander A. Leukotriene D 4-induced activation and translocation of the G-protein α 13-subunit in human epithelial cells. Biochem Biophys Res Commun 1996; 226: 413–419], the signalling pathway further downstream is still unclear. In the present study, we investigated the possible involvement of CAMP and protein kinase A activity in the LTD 4-induced Ca +2, influx in the epithelial cell line Int 407. Stimulation with LTD 4, but not with the calcium ionophore ionomycin, triggered a rapid increase (peak at 7 s) in the cellular CAMP level, an effect that was totally abolished by pertussis toxin. Furthermore, the LTD 4-induced Ca 2+ signal was reduced by 60% when cells that had been pre-incubated with the protein kinase A inhibitor Rp-cAMPS (50 μM for 30 min) were stimulated in a calcium containing medium. In contrast, Rp-cAMPS had no apparent effect on the LTD 4-induced Ca 2+ signal when the cells were stimulated in a calcium-depleted medium. The immediate LTD 4-induced protein tyrosine phosphorylation (15 s), previously shown to be necessary for the subsequent Ca 2+ influx, was abolished not only by pretreatment with pertussis toxin but also by exposure to Rp-cAMPS. Furthermore, direct activation of the cellular adenylyl cyclase activity by treatment with forskolin alone induced a prompt Ca 2+-signal in the presence, but not in the absence, of extracellular Ca 2+ identical results were obtained with the cell permeable cAMP analogue 8-bromo-cAMP. In addition, forskolin induced protein tyrosine phosphorylation similar to that seen with LTD 4. These results suggest that protein kinase A activity participates in the regulation of the LTD 4-induced Ca 2+ influx at a site that is downstream of the activation of the pertussis toxin-sensitive G-protein but upstream of a LTD 4-stimulated tyrosine kinase(s).

Density of Guanine Nucleotide-Binding Proteins in Platelets of Patients with Major Depression: Increased Abundance of the Gα i2 Subunit and Down-Regulation by Antidepressant Drug Treatment

The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein subunits (inhibitory Gα i, stimulatory Gα s, Gα q/11, and Gβ) in platelets of unipolar depressed patients to assess the status of these signal transduction proteins in depression and the effects of antidepressant drug treatment. Blood platelets were collected from 22 drug-free depressed patients and 22 age- and sex-matched healthy controls. The levels of the various G protein subunits were assessed by immunoblotting techniques. The immunoreactivity of Gα i2 was increased (41%) and that of Gα i3 decreased (25%) in platelets of depressed patients. The levels of other G protein subunits (Gα s, Gα q/11, Gβ) did not change significantly with respect to those of control subjects. Chronic administration of cyclic antidepressant drugs (citalopram, clomipramine, imipramine) decreased the immunoreactivity of the up-regulated Gα i2 protein (31%). Since platelet Gα i2 proteins mediate the signaling of α 2A-adrenoceptors, the higher expression of Gα i2 is in line with the existence of supersensitivity of these receptors in major depression.

Age-dependent increases in protein kinase C-αβ immunoreactivity and activity in the human brain: possible in vivo modulatory effects on guanine nucleotide regulatory G i proteins

In the postmortem human brain (20 specimens of frontal cortex, Brodmann area 9) the abundance of immunoreactive protein kinase C (PKC-αβ) and the activity of PKC (calcium, phosphatidylserine, and phorbol ester-dependent enzymes) were determined to study the effect of aging (range 1 month to 89 years) on this regulatory enzyme. Also, the abundance of immunoreactive G protein subunits ( Gα i1/2 , Gα i3 , Gα o , Gα s and Gβ) were assessed in parallel to investigate possible relationships with PKC-αβ. The abundance of PKC-αβ was positively correlated with aging ( r = 0.62, n = 20, P < 0.005). Moreover, PKC activity also showed a significant positive correlation with the age of the subject at death ( r = 0.55, n = 14, P < 0.05). Because of the known in vitro modulatory role of PKC-αβ on G 1 proteins, the existence of an in vivo effect of brain PKC-αβ on various G proteins was assessed through correlation analyses. In the brain of the same subjects, there were significant negative correlations between the immunoreactivity of PKC-αβ and the immunoreactivities of Gα i1/2 , ( r = −0.78, n = 13, P < 0.005) and Gα i3 ( r = −0.58, n = 15, P < 0.005). In the same brains, similar negative, although non-significant, correlations were found between the levels of PKC-αβ and those of Gα o , Gα s and Gβ. The results demonstrate an up-regulation of brain PKC-αβ with aging and suggest the existence of a relevant in vivo modulatory role of this regulatory enzyme on inhibitory G i proteins in the human brain during the process of aging.

Generation of inositol phosphates in bitter taste transduction

It is probable that there is a diversity of mechanisms involved in the transduction of bitter taste. One of these mechanisms uses the second messengers, inositol 1,4,5-trisphosphate (IP 3) and diacylglycerol (DAG). Partial membrane preparations from circumvallate and foliate taste regions of mice tongues responded to the addition of known bitter taste stimuli by increasing the amount of inositol phosphates produced after 30 s incubation. Addition of both the bitter stimulus, sucrose octaacetate and the G-protein stimulant, GTPγS, led to an enhanced production of inositol phosphates compared with either alone. Pretreatment of the tissue samples with pertussis toxin eliminated all response to sucrose octaacetate plus GTPγS, whereas pretreatment with cholera toxin was without effect. Western blots of solubilized tissue from circumvallate and foliate regions probed with antibodies to the α-subunit of several types of G-proteins revealed bands reactive to antibodies against Gα i1–2 and Gα o, with no apparent activity to antibodies against Gα i3. Given the results from the immunoblots and those of the toxin experiments, it is proposed that the transduction of the bitter taste of sucrose octaacetate in mice involves a receptor-mediated activation of a G i-type protein which activates a phospholipase C to produce the two second messengers, IP 3 and DAG.

The fusion pore interface: a new biological frontier

The development of micro-voltammetry to detect the release of secretory products from single cells has yielded surprising information, which suggests that the release of secretory products is regulated after the fusion of secretory vesicles with the plasma membrane. This technique has also been used to demonstrate that the release of secretory products can occur during transient fusion events, which leads one to question the current models for membrane recycling. In the past year, strong evidence has emerged in support of a role for rab3 and Gα i3 proteins in regulating a putative scaffold of proteins that cause bilayer fusion during exocytosis. These findings parallel the biochemical identification of several new cytosolic, secretory vesicle and plasma membrane proteins that may also play a role in regulating fusion.

Opioid-induced supraspinal antinociception in mice is mediated by [formula omitted] (μ) and G 13 (δ) transducer proteins

Polyclonal antisera (purified IgGs) raised against specific sequences of Gα proteins (G X/Z , G i1 , G i2 , G i3 ) were injected intracerebroventricularly (i.c.v,) at dilutions ≥1:1,000 and opioid-induced antinociceptive dose-response curves were subsequently constructed 24 h later. IgGs anti G i2 α reduced the activity of all the opioids studied, (DAMGO, morphine, β-endorphin, DADLE, DPDPE and [D-Ala 2 ] Deltorphin II). Anti Gα i3 impaired the activity of β-endorphin, DADLE, DPDPE and [D-Ala 2 ] Deltorphin II, whereas anti G il α sera were devoid of effect

Signal-transducing G proteins and antidepressant Drugs: Evidence for modulation of α subunit gene expression in rat brain

Signal-transducing G proteins, heterotrimers formed of α, β, and γ subunits, are central to the coordination of receptor-effector communication. They are derived from a large gene family, and recent cloning and sequencing of cDNAs encoding the α subunits, which confer receptor and effector specificity on the heterotrimer, have defined four major classes, G s, G i, G q, and G 12, with at least 16 isotopes. The G proteins that coordinate receptor-effector activity are especially important in the central nervous system (CNS), where they serve widespread, critical roles in the regulation of neuronal function, maintain the functional balance between neurotransmitter systems, and, as such, represent attractive potential targets for antidepressant drugs. We describe an integrated series of animal and cell culture studies aimed at testing the hypothesis that alterations in G protein function may contribute the complex neuroadaptive mechanisms involved in the clinical actions of antidepressants, and demonstrate that long-term administration of a wide spectrum of antidepressant drugs regulate Gα s , Gα i1 , Gα i2 , Gα o , Gα q , and Gα 12 mRNA and protein expression in various areas of the rat brain. Additionally, we present the polymerase chain reaction-(PCR) mediated cross-species partial cDNA cloning and sequencing of rat and human Gα o and rat G α 12, illustrate the regional distribution of Gα mRNA and protein in rat brain, and provide evidence that different classes of antidepressants alter expression and/or stability of the recently identified Gα 12 mRNA. We conclude that long-term treatment with antidepressant drugs exerts differential effects on Gα mRNA and protein expression in rat brain, thus modifying signal transduction as an integral part of complex neuroadaptive mechanisms that may underlie their therapeutic efficacy. The development of novel drugs with G proteins as primary targets remains an attractive prospect for the future.

Beta-adrenergic receptors and their mode of coupling to adenylate cyclase

articleBeta-adrenergic receptors and their mode of coupling to adenylate cyclaseA. LevitzkiA. LevitzkiPublished Online:01 Jul 1986https://doi.org/10.1152/physrev.1986.66.3.819MoreSectionsPDF (5 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Download PDF FiguresReferencesRelatedInformationCited ByCombining resonance energy transfer methods reveals a complex between the α 2A -adrenergic receptor, Gα i1 β 1 γ 2 , and GRK2The FASEB Journal, Vol. 24, No. 12Genesis and Regulation of the Heart AutomaticityMatteo E. Mangoni, and Joël Nargeot1 July 2008 | Physiological Reviews, Vol. 88, No. 3Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and DiseaseGordon S. Lynch, and James G. Ryall1 April 2008 | Physiological Reviews, Vol. 88, No. 2Cholesterol as a determinant of cooperativity in the M2 muscarinic cholinergic receptorBiochemical Pharmacology, Vol. 74, No. 2Effects of β2-agonist administration and exercise on contractile activation of skeletal muscle fibersGordon S. Lynch, Alan Hayes, Siun P. Campbell, and David A. Williams1 October 1996 | Journal of Applied Physiology, Vol. 81, No. 4Unoccupied β-adrenoceptor-induced adenylyl cyclase stimulation in turkey erythrocyte membranesEuropean Journal of Pharmacology: Molecular Pharmacology, Vol. 268, No. 2Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes.Circulation Research, Vol. 72, No. 3The signal transduction between β-receptors and adenylyl cyclaseLife Sciences, Vol. 52, No. 26Positive inotropic effects of CGRP and isoprenaline: Analogies and differencesNeuropeptides, Vol. 23, No. 3Effect of albumin on adenylate cyclase receptor-related signal transduction of human peripheral blood mononuclear cellsBiochemical Pharmacology, Vol. 44, No. 2Alpha-1 adrenergic receptor number and receptor density in isolated hepatocytes from foetal, juvenile and adult ratsCellular Signalling, Vol. 4, No. 3Critique2 July 2016 | Journal of Psychopharmacology, Vol. 6, No. 1Interaction betweenα2- and β-adrenergic receptors in rat cerebral cortical membranes: clonidine-induced reduction in agonist and antagonist affinity for β-adrenergic receptorsBrain Research, Vol. 542, No. 2The regulation of adenylyl cyclase by receptor-operated G proteinsPharmacology & Therapeutics, Vol. 50, No. 3Rhythms in second messenger mechanismsPharmacology & Therapeutics, Vol. 51, No. 2Effect of oxygen tension on catecholamine-induced formation of cAMP and on swelling of carp red blood cellsA. Salama, and M. Nikinmaa1 November 1990 | American Journal of Physiology-Cell Physiology, Vol. 259, No. 5The effect of aluminum on markers for synaptic neurotransmission, cyclic AMP, and neurofilaments in a neuroblastoma × glioma hybridoma (NG108-15)Brain Research, Vol. 528, No. 1Biochemical and autoradiographic analysis of β-adrenoceptors in rat nasal mucosaEuropean Journal of Pharmacology, Vol. 182, No. 3Sites and mechanisms of Ca2+ movement in non-excitable cellsCell Calcium, Vol. 10, No. 5Optimal features of a new β-blockerAmerican Heart Journal, Vol. 116, No. 5Functional ß-adrenergic receptors in a human mammary cell line (HBL-100)Biochemical Pharmacology, Vol. 37, No. 15Transmembrane signalling to adenylate cyclase in mammalian cells and in Saccharomyces cerevisiaeTrends in Biochemical Sciences, Vol. 13, No. 8A potassium conductance contributes to the action of somatostatin-14 to suppress ACTH secretionBrain Research, Vol. 444, No. 2Regulation of cardiac ion channels by catecholamines, acetylcholine and second messenger systemsProgress in Biophysics and Molecular Biology, Vol. 52, No. 3Central adrenergic receptors2 July 2016 | Journal of Psychopharmacology, Vol. 1, No. 2 More from this issue > Volume 66Issue 3July 1986Pages 819-854 Copyright & PermissionsCopyright © 1986 the American Physiological Societyhttps://doi.org/10.1152/physrev.1986.66.3.819PubMed3016770History Published online 1 July 1986 Published in print 1 July 1986 Metrics