Evidence for a role of protein kinase-C in His-D-Trp-Ala-Trp-D-Phe-Lys-NH2-induced growth hormone release from rat primary pituitary cells
Autor: | Wanda W.-S. Chan, Bridget Butler, Roy G. Smith, Albert Barreto, Rang Cheng |
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Rok vydání: | 1991 |
Předmět: |
Male
medicine.medical_specialty Pituitary gland Phloretin Molecular Sequence Data Biology Growth Hormone-Releasing Hormone chemistry.chemical_compound Endocrinology Internal medicine medicine Cyclic AMP Animals GHRP-6 Amino Acid Sequence Protein kinase C Calcimycin Protein Kinase C Forskolin Colforsin Drug Synergism Rats Inbred Strains Rats Somatropin medicine.anatomical_structure chemistry Mechanism of action Growth Hormone Pituitary Gland Phorbol Tetradecanoylphorbol Acetate medicine.symptom Oligopeptides |
Zdroj: | Endocrinology. 129(6) |
ISSN: | 0013-7227 |
Popis: | We have recently reported that His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) synergizes with GH-releasing factor (GRF) to increase GH release and cAMP accumulation in rat pituitary cells in vitro. This study was undertaken to further investigate the mechanism of action of GHRP-6 on GH release, particularly the involvement of protein kinase-C. Forskolin (10(-5) M), A23187 (10(-6) M), and phorbol 12-myristate 13-acetate (PMA; 10(-7) M) all stimulated GH release. However, only PMA can mimic the synergistic effects of GHRP-6 on GRF-stimulated GH release and intracellular cAMP accumulation. 4 alpha-Phorbol 12,13-didecanoate, an inactive phorbol ester, was unable to stimulate GH release or potentiate the effect of GRF. Extracellularly added phospholipase-C not only stimulated GH release in a dose-dependent manner, but also potentiated GRF-induced GH release. Phloretin, a protein kinase-C inhibitor, in a concentration range of 10-250 microM had very little or no effect on basal and GRF-stimulated GH release, but markedly inhibited the stimulatory effects induced by either PMA or GHRP-6. Incubation of rat pituitary cells with 10(-6) M PMA for 24 h completely down-regulated protein kinase-C, since such PMA-pretreated cells did not release GH in response to a second dose of PMA. The protein kinase-C-depleted cells had an attenuated GHRP-6 response, but they responded normally to GRF. Moreover, the synergistic effects of GHRP-6 and GRF on GH release and cAMP accumulation were also greatly inhibited by protein kinase-C down-regulation. These data suggest that the effects of GHRP-6 on GH release, either alone or together with GRF, are at least partially mediated via the activation of protein kinase-C. |
Databáze: | OpenAIRE |
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