G Protein Activation and Cyclic AMP Modulation by Naloxone Benzoylhydrazone in Distinct Layers of Rat Olfactory Bulb

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2004 Sep 29

PMID 15451772

Citations 5

Authors

Pierluigi Onali

Maria C Olianas

Affiliations

Soon will be listed here.

Abstract

1 Naloxone benzoylhydrazone (NalBzoH) has initially been developed as an agonist of the pharmacologically defined kappa3-opioid receptor and has recently been employed as an antagonist at the opioid receptor-like (ORL1) receptor. In the present study, we investigated the ability of NalBzoH to elicit agonist-like effects on receptor signalling in distinct layers of rat olfactory bulb, a brain region where we have demonstrated the presence of opioid and ORL1 receptors coupled to both stimulation and inhibition of cyclic AMP formation. 2 In membranes of the olfactory nerve-glomerular layer (ON-GL), external plexiform layer (EPL) and granule cell layer (GRL), NalBzoH elicited a concentration-dependent stimulation of guanosine-5'-O-(3-[35S]-thio)triphosphate ([35S]GTPgammaS) binding with pEC50 values ranging from 7.36 to 7.86, whereas the kappa1-opioid receptor agonists (-)-U-50,488 and U-69,593 were inactive. 3 In membranes of GRL, but not ON-GL and EPL, NalBzoH stimulated basal adenylyl cyclase activity by 40% with a pEC50 of 8.14, and significantly potentiated the net enzyme stimulation elicited by corticotropin-releasing hormone and pituitary adenylate cyclase-activating peptide 38. Pertussis toxin prevented the NalBzoH stimulations of [35S]GTPgammaS binding and adenylyl cyclase activity. 4 In membranes of EPL and GRL, but not ON-GL, NalBzoH elicited a concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase activity with pEC50 values of 8.07 and 8.08, respectively. 5 At concentrations that completely blocked the actions of nociceptin/orphanin FQ (N/OFQ), the ORL1 receptor antagonists CompB and [Nphe1]N/OFQ(1-13)NH2 failed to antagonize either the stimulatory or the inhibitory effect of NalBzoH on cyclic AMP formation. Similarly, the kappa1-opioid receptor antagonist nor-binaltorphimine counteracted the NalBzoH effects with relatively low potencies (pKi values=7.67-8.09). 6 Conversely, the selective delta-opioid receptor antagonist TIPP (pKi=9.10) and the selective mu-opioid receptor antagonist CTAP (pKi=8.27) reduced the inhibitory effect of NalBzoH by 70 and 30%, respectively. Moreover, TIPP and CTAP potently inhibited the NalBzoH stimulation of cyclic AMP, each antagonist maximally causing 50% blockade of the agonist response. 7These data demonstrate that in the olfactory bulb NalBzoH activates receptor signalling by acting through delta- and mu-opioid receptors and independently of ORL1 and kappa1-opioid receptors.

Citing Articles

Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders.

Burns J, Kroll D, Feldman D, Kure Liu C, Manza P, Wiers C Front Psychiatry. 2019; 10:626.

PMID: 31620026 PMC: 6759955. DOI: 10.3389/fpsyt.2019.00626.

Molecular Pharmacology of δ-Opioid Receptors.

Gendron L, Cahill C, Von Zastrow M, Schiller P, Pineyro G Pharmacol Rev. 2016; 68(3):631-700.

PMID: 27343248 PMC: 4931872. DOI: 10.1124/pr.114.008979.

G protein-coupled receptor heteromerization: a role in allosteric modulation of ligand binding.

Gomes I, IJzerman A, Ye K, Maillet E, Devi L Mol Pharmacol. 2011; 79(6):1044-52.

PMID: 21415307 PMC: 3102551. DOI: 10.1124/mol.110.070847.

Agonist activity of naloxone benzoylhydrazone at recombinant and native opioid receptors.

Olianas M, Concas D, Onali P Br J Pharmacol. 2006; 147(4):360-70.

PMID: 16402046 PMC: 1616995. DOI: 10.1038/sj.bjp.0706601.

Has the sun set on kappa3-opioid receptors?.

Connor M, Kitchen I Br J Pharmacol. 2006; 147(4):349-50.

PMID: 16402044 PMC: 1616993. DOI: 10.1038/sj.bjp.0706603.

References

Cheng J, Roques B, Gacel G, Huang E, Pasternak G . Kappa 3 opiate receptor binding in the mouse and rat. Eur J Pharmacol. 1992; 226(1):15-20. DOI: 10.1016/0922-4106(92)90077-9. View

Schiller P, Nguyen T, Weltrowska G, Wilkes B, Marsden B, Lemieux C . Differential stereochemical requirements of mu vs. delta opioid receptors for ligand binding and signal transduction: development of a class of potent and highly delta-selective peptide antagonists. Proc Natl Acad Sci U S A. 1992; 89(24):11871-5. PMC: 50659. DOI: 10.1073/pnas.89.24.11871. View

Cruciani R, Dvorkin B, Morris S, Crain S, MAKMAN M . Direct coupling of opioid receptors to both stimulatory and inhibitory guanine nucleotide-binding proteins in F-11 neuroblastoma-sensory neuron hybrid cells. Proc Natl Acad Sci U S A. 1993; 90(7):3019-23. PMC: 46228. DOI: 10.1073/pnas.90.7.3019. View

Olianas M, Onali P . Activation of opioid and muscarinic receptors stimulates basal adenylyl cyclase but inhibits Ca2+/calmodulin- and forskolin-stimulated enzyme activities in rat olfactory bulb. J Neurochem. 1994; 63(1):161-8. DOI: 10.1046/j.1471-4159.1994.63010161.x. View

Standifer K, Cheng J, Brooks A, Honrado C, Su W, Visconti L . Biochemical and pharmacological characterization of mu, delta and kappa 3 opioid receptors expressed in BE(2)-C neuroblastoma cells. J Pharmacol Exp Ther. 1994; 270(3):1246-55. View

Mansour A, Fox C, Akil H, Watson S . Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends Neurosci. 1995; 18(1):22-9. DOI: 10.1016/0166-2236(95)93946-u. View

Cheng J, Standifer K, Tublin P, Su W, Pasternak G . Demonstration of kappa 3-opioid receptors in the SH-SY5Y human neuroblastoma cell line. J Neurochem. 1995; 65(1):170-5. DOI: 10.1046/j.1471-4159.1995.65010170.x. View

Pan Y, Cheng J, Xu J, Rossi G, Jacobson E, Brooks A . Cloning and functional characterization through antisense mapping of a kappa 3-related opioid receptor. Mol Pharmacol. 1995; 47(6):1180-8. View

Kinsley C, Morse A, Zoumas C, Corl S, Billack B . Intracerebroventricular infusions of morphine, and blockade with naloxone, modify the olfactory preferences for pup odors in lactating rats. Brain Res Bull. 1995; 37(1):103-7. DOI: 10.1016/0361-9230(94)00263-0. View

10.

Prather P, McGinn T, Claude P, Liu-Chen L, Loh H, Law P . Properties of a kappa-opioid receptor expressed in CHO cells: interaction with multiple G-proteins is not specific for any individual G alpha subunit and is similar to that of other opioid receptors. Brain Res Mol Brain Res. 1995; 29(2):336-46. DOI: 10.1016/0169-328x(94)00264-f. View

11.

Meunier J, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P . Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature. 1995; 377(6549):532-5. DOI: 10.1038/377532a0. View

12.

Reinscheid R, Nothacker H, Bourson A, Ardati A, Henningsen R, Bunzow J . Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science. 1995; 270(5237):792-4. DOI: 10.1126/science.270.5237.792. View

13.

White A, Polgar W, DeCosta B, Pasternak G, Toll L . The in vitro pharmacological characterization of naloxone benzoylhydrazone. Eur J Pharmacol. 1995; 277(2-3):257-63. DOI: 10.1016/0014-2999(95)00088-3. View

14.

Sunahara R, Dessauer C, GILMAN A . Complexity and diversity of mammalian adenylyl cyclases. Annu Rev Pharmacol Toxicol. 1996; 36:461-80. DOI: 10.1146/annurev.pa.36.040196.002333. View

15.

Wang L, Gintzler A . Altered mu-opiate receptor-G protein signal transduction following chronic morphine exposure. J Neurochem. 1997; 68(1):248-54. DOI: 10.1046/j.1471-4159.1997.68010248.x. View

16.

Dhawan B, Cesselin F, Raghubir R, Reisine T, Bradley P, Portoghese P . International Union of Pharmacology. XII. Classification of opioid receptors. Pharmacol Rev. 1996; 48(4):567-92. View

17.

Abdulla F, Smith P . Nociceptin inhibits T-type Ca2+ channel current in rat sensory neurons by a G-protein-independent mechanism. J Neurosci. 1997; 17(22):8721-8. PMC: 6573070. View

18.

Noda Y, Mamiya T, Nabeshima T, Nishi M, Higashioka M, Takeshima H . Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice. J Biol Chem. 1998; 273(29):18047-51. DOI: 10.1074/jbc.273.29.18047. View

19.

Mori K, Nagao H, Yoshihara Y . The olfactory bulb: coding and processing of odor molecule information. Science. 1999; 286(5440):711-5. DOI: 10.1126/science.286.5440.711. View

20.

Nabeshima T, Noda Y, Mamiya T . The role of nociceptin in cognition. Brain Res. 1999; 848(1-2):167-73. DOI: 10.1016/s0006-8993(99)01906-x. View