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Microinjection of a selective kappa opioid agonist into the supraoptic nucleus (SON) increases inducible cAMP element repressor (ICER) expression
Author(s) -
Gottlieb Helmut,
Martinez Michelle,
Ji Lisa,
Cunningham JT
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1159.1
Subject(s) - microinjection , endocrinology , medicine , agonist , κ opioid receptor , chemistry , supraoptic nucleus , receptor , hypothalamus
Administration of kappa opioid (κ) agonists in conscious rats produce diuresis via central inhibition of vasopressin (AVP) neurons in the SON and paraventricular nucleus of the hypothalamus, but the molecular mechanism is unknown. Activation of κ receptors produces an inhibition of cAMP accumulation via G i/o proteins. However, pre‐treatment with pertussis toxin (an inhibitor of G i/o ) fails to block the κ effects in the SON. This suggests that activation of other transcriptions factors may participate in cAMP inhibition (i.e., ICER). This study examined changes in ICER staining following direct microinjection of a selective κ opioid agonist, U50‐488H (U50), into the SON of conscious rats. The forebrain was processed for ICER using polyclonal anti‐ICER antibody raised in rabbit. Microinjection of U50 elicited significant increases in ICER staining in the SON (C, 35 ± 4; U50, 64 ± 5; P < .05). In addition, double labeling shows significant increase in AVP/ICER staining as compared to control (C, 11 ± 1; U50, 22 ± 2; P<.05). This is the first study to show direct activation of ICER by κ. In addition, U50 preferentially increased ICER expression in AVP neurons and not in oxytocin neurons. These results suggest a novel pathway for κ opioid‐mediated suppression of cAMP accumulation, AVP neurons inhibition, and suppression of AVP secretion that is independent of G i/o . Supported by NIH HL62579 & DK57822.