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Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission.
J Neurosci 2014; 34(24):8324-32JN

Abstract

Action potentials trigger synaptic terminals to synchronously release vesicles, but some vesicles release spontaneously. G-protein-coupled receptors (GPCRs) can modulate both of these processes. At cranial primary afferent terminals, the GPCR cannabinoid 1 (CB1) is often coexpressed with transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel present on most afferents. Here we tested whether CB1 activation modulates synchronous, action potential-evoked (eEPSCs) and/or spontaneous (sEPSCs) EPSCs at solitary tract nucleus neurons. In rat horizontal brainstem slices, activation of solitary tract (ST) primary afferents generated ST-eEPSCs that were rapidly and reversibly inhibited from most afferents by activation of CB1 with arachidonyl-2'-chloroethylamide (ACEA) or WIN 55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate]. The CB1 antagonist/inverse agonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] blocked these responses. Despite profound depression of ST-eEPSCs during CB1 activation, sEPSCs in these same neurons were unaltered. Changes in temperature changed sEPSC frequency only from TRPV1(+) afferents (i.e., thermal sEPSC responses only occurred in TRPV1(+) afferents). CB1 activation failed to alter these thermal sEPSC responses. However, the endogenous arachidonate metabolite N-arachidonyldopamine (NADA) promiscuously activated both CB1 and TRPV1 receptors. NADA inhibited ST-eEPSCs while simultaneously increasing sEPSC frequency, and thermally triggered sEPSC increases in neurons with TRPV1(+) afferents. We found no evidence for CB1/TRPV1 interactions suggesting independent regulation of two separate vesicle pools. Together, these data demonstrate that action potential-evoked synchronous glutamate release is modulated separately from TRPV1-mediated glutamate release despite coexistence in the same central terminations. This two-pool arrangement allows independent and opposite modulation of glutamate release by single lipid metabolites.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239 fawley.jessica@gmail.com.Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239.Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24920635

Citation

Fawley, Jessica A., et al. "Cannabinoid 1 and Transient Receptor Potential Vanilloid 1 Receptors Discretely Modulate Evoked Glutamate Separately From Spontaneous Glutamate Transmission." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 34, no. 24, 2014, pp. 8324-32.
Fawley JA, Hofmann ME, Andresen MC. Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission. J Neurosci. 2014;34(24):8324-32.
Fawley, J. A., Hofmann, M. E., & Andresen, M. C. (2014). Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 34(24), pp. 8324-32. doi:10.1523/JNEUROSCI.0315-14.2014.
Fawley JA, Hofmann ME, Andresen MC. Cannabinoid 1 and Transient Receptor Potential Vanilloid 1 Receptors Discretely Modulate Evoked Glutamate Separately From Spontaneous Glutamate Transmission. J Neurosci. 2014 Jun 11;34(24):8324-32. PubMed PMID: 24920635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission. AU - Fawley,Jessica A, AU - Hofmann,Mackenzie E, AU - Andresen,Michael C, PY - 2014/6/13/entrez PY - 2014/6/13/pubmed PY - 2014/8/5/medline KW - CB1 KW - NADA KW - NTS KW - TRPV1 KW - vesicle pool SP - 8324 EP - 32 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 34 IS - 24 N2 - Action potentials trigger synaptic terminals to synchronously release vesicles, but some vesicles release spontaneously. G-protein-coupled receptors (GPCRs) can modulate both of these processes. At cranial primary afferent terminals, the GPCR cannabinoid 1 (CB1) is often coexpressed with transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel present on most afferents. Here we tested whether CB1 activation modulates synchronous, action potential-evoked (eEPSCs) and/or spontaneous (sEPSCs) EPSCs at solitary tract nucleus neurons. In rat horizontal brainstem slices, activation of solitary tract (ST) primary afferents generated ST-eEPSCs that were rapidly and reversibly inhibited from most afferents by activation of CB1 with arachidonyl-2'-chloroethylamide (ACEA) or WIN 55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate]. The CB1 antagonist/inverse agonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] blocked these responses. Despite profound depression of ST-eEPSCs during CB1 activation, sEPSCs in these same neurons were unaltered. Changes in temperature changed sEPSC frequency only from TRPV1(+) afferents (i.e., thermal sEPSC responses only occurred in TRPV1(+) afferents). CB1 activation failed to alter these thermal sEPSC responses. However, the endogenous arachidonate metabolite N-arachidonyldopamine (NADA) promiscuously activated both CB1 and TRPV1 receptors. NADA inhibited ST-eEPSCs while simultaneously increasing sEPSC frequency, and thermally triggered sEPSC increases in neurons with TRPV1(+) afferents. We found no evidence for CB1/TRPV1 interactions suggesting independent regulation of two separate vesicle pools. Together, these data demonstrate that action potential-evoked synchronous glutamate release is modulated separately from TRPV1-mediated glutamate release despite coexistence in the same central terminations. This two-pool arrangement allows independent and opposite modulation of glutamate release by single lipid metabolites. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/24920635/Cannabinoid_1_and_transient_receptor_potential_vanilloid_1_receptors_discretely_modulate_evoked_glutamate_separately_from_spontaneous_glutamate_transmission_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=24920635 DB - PRIME DP - Unbound Medicine ER -