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Effects of Ethanol on Basal and Prostaglandin E1‐Induced Increases in β‐Endorphin Release and Intracellular cAMP Levels in Hypothalamic Cells
Author(s) -
Boyadjieva Nadka Iv.,
Sarkar Dipak K.
Publication year - 1997
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1997.tb04245.x
Subject(s) - forskolin , medicine , endocrinology , basal (medicine) , prostaglandin , ethanol , prostaglandin e , chemistry , secretion , hypothalamus , prostaglandin e2 , intracellular , desensitization (medicine) , biology , stimulation , receptor , biochemistry , insulin
Our recent studies determining the effect of cAMP‐elevating agents forskolin and dibutyryl cAMP on ethanol‐induced immunoreactive p‐endorphin (IR‐β‐EP) release from hypothalamic cells in primary cultures suggested the possibility that both stimulatory and adaptive secretory responses of β‐EP neurons after ethanol exposure may involve the cAMP system. To determine further the role of cAMP, the effects of prostaglandin E1 (PGE1) on basal and ethanol‐regulated IR‐β‐EP secretion and cAMP productions were determined in primary cultures of hypothalamic cells. The results presented in this study show that a 50 mM dose of ethanol, which is within the EC 50 dose of ethanol required to elevate IR‐β‐EP release from hypothalamic cells, increased cellular levels of cAMP and elevated IR‐β‐EP release simultaneously from the cultured neurons for a period of 6 hr. The cAMP and IR‐β‐EP secretory responses developed desensitization to ethanol challenge after 24 hr of constant ethanol incubation. The cAMP‐elevating agent PGE1 increased the cellular content of cAMP and IR‐β‐EP release in a dose‐dependent manner. The EC 50 dose of PGE1 for elevation of IR‐β‐EP and cAMP was ∼0.5 μM. As with ethanol, chronic treatment with PGE1 desensitized the cAMP and IR‐β‐EP responses of hypothalamic neurons to PGE1. Acute exposure to ethanol increased the PGE1 ‐stimulated levels of cAMP and IR‐β‐EP, whereas chronic exposure to ethanol resulted in diminished cAMP responses to PGE1. These data provide evidence that the cAMP system may be involve in controlling hypothalamic β‐EP secretion, as well in regulating the stimulatory and adaptive responses of β‐EP neurons to ethanol.