Cannabinoid CB1 Receptor-Mediated Inhibition of Prolactin Release and Signaling Mechanisms in GH4C1 Cells*
| Autor: | Begonia Y Ho, Paul L. Prather, Wai-Meng Kwok, Zeljko J. Bosnjak, Anna Stadnicka, Lori L. Current, Arthur R. Buckley |
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| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Cannabinoid receptor GTP' Morpholines Receptors Drug medicine.medical_treatment Nisoldipine chemistry.chemical_element Photoaffinity Labels Naphthalenes Calcium Biology Pharmacology Pertussis toxin Endocrinology GTP-Binding Proteins Internal medicine Tumor Cells Cultured Cannabinoid receptor type 2 medicine Animals Pituitary Neoplasms Secretion Receptors Cannabinoid Cannabinoids Calcium channel Calcium Channel Blockers Benzoxazines Prolactin Rats chemistry Type C Phospholipases Calcium Channels Cannabinoid Adenylyl Cyclases Signal Transduction |
| Zdroj: | Endocrinology. 141:1675-1685 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | The GH4C1 cell line was used to study the cellular mechanisms of cannabinoid-mediated inhibition of PRL release. Cannabinoid CB1 receptor activation inhibited vasoactive intestinal polypeptide- and TRH-stimulated PRL release, but not its basal secretion. The cannabinoid-mediated inhibition of TRH-stimulated PRL release was reversed by the CB1 receptor-specific antagonist, SR141,716A, and was abolished by pertussis toxin pretreatment, indicating that G alpha subunits belonging to the G(i)alpha and G(o)alpha family were involved in the signaling. Photoaffinity labeling using [alpha-32P] azidoaniline GTP showed that cannabinoid receptor stimulation in cell membranes produced activation of four G alpha subunits (G(i)alpha2, G(i)alpha3, G(o)alpha1, and G(o)alpha2), which was also reversed by SR141,716A. The CB1 receptor agonists, WIN55,212-2 and CP55,940, inhibited cAMP formation and calcium currents in GH4C1 cells. The subtypes of calcium currents inhibited by WIN55,212-2 were characterized using holding potential sensitivity and calcium channel blockers. WIN55,212-2 inhibited the omega-conotoxin GVIA (Conus geographus)- and omega-agatoxin IVA (Aigelenopsis aperta)-sensitive calcium currents, but not the nisoldipine-sensitive calcium currents, suggesting the inhibition of N- and P-type, but not L-type, calcium currents. Taken together, the present findings indicate that CB1 receptors can couple through pertussis toxin-sensitive G alpha subunits to inhibit adenylyl cyclase and calcium currents and suppress PRL release from GH4C1 cells. |
| Databáze: | OpenAIRE |
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