The vasodepressor mechanism of action of 2-(l-octynyl)-adenosine, a novel adenosine A2 receptor agonist, does not involve inhibitory G protein in rats

We used the whole cell open-patch or perforated-patch technique to characterize μ-opioid modulation of Ca2+ current ( I Ca) in nodose sensory neurons and in a specific subpopulation of nodose cells, aortic baroreceptor neurons. The μ-opiate receptor agonist Tyr-d-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) inhibited I Ca in 95% of neonatal [postnatal day (P)1–P3] nodose neurons. To the contrary, only 64% of juvenile cells (P20–P35) and 61% of adult cells (P60–P110) responded to DAGO. DAGO-mediated inhibition of I Ca was naloxone sensitive, irreversible in the presence of guanosine 5′- O-(3-thiotriphosphate), absent with guanosine 5′- O-(2-thiodiphosphate), and eliminated with pertussis toxin; DAGO’s inhibition of I Ca was G protein mediated. Incubation of neurons with ω-conotoxin GVIA eliminated the effect of DAGO in neonatal but not in juvenile cells. In the latter, DAGO reduced 37% of the current remaining in the presence of ω-conotoxin. In the subset of nodose neurons, aortic baroafferents, the effect of DAGO was concentration dependent, with an IC50 of 1.82 × 10−8 M. DAGO slowed activation of I Ca, but activation curves constructed from tail currents were the same with and without DAGO (100 nM). In summary, μ-opiate modulation of I Ca in nodose neurons was demonstrated in three age groups, including specifically labeled baroafferents. The demonstration of a mechanism of action of μ-opioids on baroreceptor afferents provides a basis for the attenuation of the baroreflex that occurs at the level of the nucleus tractus solitarii.

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An adenosine receptor agonist-induced modulation of TSH-dependent cell growth in FRTL-5 thyroid cells mediated by inhibitory G protein, Gi

Biochimie ◽

10.1016/s0300-9084(99)80079-0 ◽

1999 ◽

Vol 81 (4) ◽

pp. 341-346 ◽

Cited By ~ 5

Author(s):

Kimie Sho ◽

Torao Narita ◽

Fumikazu Okajima ◽

Yoichi Kondo

Keyword(s):

Cell Growth ◽

G Protein ◽

Adenosine Receptor ◽

Receptor Agonist ◽

Thyroid Cells ◽

Adenosine Receptor Agonist ◽

Dependent Cell ◽

Inhibitory G Protein

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The G protein-biased kappa opioid receptor agonist 6′-GNTI blocks hippocampal paroxysmal discharges without inducing aversion

Intrinsic Activity ◽

10.25006/ia.3.s2-a2.14 ◽

2015 ◽

Vol 3 (Suppl. 2) ◽

pp. A2.14

Author(s):

Luca Zangrandi

Keyword(s):

G Protein ◽

Opioid Receptor ◽

Receptor Agonist ◽

Kappa Opioid Receptor ◽

Kappa Opioid ◽

Opioid Receptor Agonist

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Isoprenylation of an inhibitory G protein alpha subunit occurs only upon mutagenesis of the carboxyl terminus.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)45381-6 ◽

1990 ◽

Vol 265 (32) ◽

pp. 19389-19392 ◽

Cited By ~ 13

Author(s):

T L Jones ◽

A M Spiegel

Keyword(s):

G Protein ◽

Alpha Subunit ◽

Carboxyl Terminus ◽

Inhibitory G Protein ◽

G Protein Alpha Subunit ◽

Protein Alpha Subunit

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Reciprocal inhibition of voltage-gated potassium currents (IK(V)) by activation of cannabinoid CB1and dopamine D1receptors in ON bipolar cells of goldfish retina

Visual Neuroscience ◽

10.1017/s0952523805221089 ◽

2005 ◽

Vol 22 (1) ◽

pp. 55-63 ◽

Cited By ~ 30

Author(s):

SHIH-FANG FAN ◽

STEPHEN YAZULLA

Keyword(s):

G Protein ◽

Receptor Agonist ◽

Lucifer Yellow ◽

Reciprocal Inhibition ◽

Receptor Activation ◽

Light Signal ◽

Bipolar Cells ◽

Protein G ◽

Calcium Dependent ◽

Voltage Dependent

Cannabinoid CB1receptor (viaGs) and dopamine D2receptor (viaGi/o) antagonistically modulate goldfish cone membrane currents. As ON bipolar cells have CB1and D1receptors, but not D2receptors, we focused on whether CB1receptor agonist and dopamine interact to modulate voltage-dependent outward membrane K+currentsIK(V)of the ON mixed rod/cone (Mb) bipolar cells. Whole-cell currents were recorded from Mb bipolar cells in goldfish retinal slices. Mb bipolar cells were identified by intracellular filling with Lucifer yellow. The bath solution was calcium-free and contained 1 mM cobalt to block indirect calcium-dependent effects. Dopamine (10 μM) consistently increasedIK(V)by a factor of 1.57 ± 0.12 (S.E.M.,n= 15). A CB receptor agonist, WIN 55212-2 (0.25–1 μM), had no effect, but 4 μM WIN 55212-2 suppressedIK(V)by 60%. IfIK(V)was first increased by 10 μM dopamine, application of WIN 55212-2 (0.25–1 μM) reversibly blocked the effect of dopamine even though these concentrations of WIN 55212-2 had no effect of their own. If WIN 55212-2 was applied first and dopamine (10 μM) was added to the WIN-containing solution, 0.1 μM WIN 55212-2 blocked the effect of dopamine. All effects of WIN 55212-2 were blocked by coapplication of SR 141716A (CB1antagonist) and pretreatment with pertussis toxin (blocker of Gi/o) indicating actionviaCB1receptor activation of G protein Gi/o. Coactivation of CB1and D1receptors on Mb bipolar cells produces reciprocal effects onIK(V). The CB1-evoked suppression ofIK(V)is mediated by G protein Gi/o, whereas the D1-evoked enhancement is mediated by G protein Gs. As dopamine is a retinal “light” signal, these data support our notion that endocannabinoids function as a “dark” signal, interacting with dopamine to set retinal sensitivity.

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