Document Detail

WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion.
MedLine Citation:
PMID:  9652368     Owner:  NLM     Status:  MEDLINE    
Previous studies suggest that the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) increases the secretion of oxytocin, adrenocorticotropic hormone (ACTH), corticosterone and prolactin but not renin. However, the lack of selective 5-HT1A receptor antagonists made it difficult to confirm that 5-HT1A receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT1A receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 microg/kg s.c., increased plasma levels of oxytocin (to 970% above basal levels); ACTH (to 1622% above basal levels), corticosterone (to 458% above basal levels) and prolactin (to 313% above basal levels), but not renin. The lowest dose of WAY-100635 (0.1 mg/kg s.c.) significantly inhibited the 8-OH-DPAT-induced increase in plasma oxytocin but not ACTH or corticosterone levels. At a dose of 1 mg/kg (s.c.), WAY-100635 completely blocked the oxytocin and ACTH responses and maximally inhibited the corticosterone response to 8-OH-DPAT, although corticosterone levels were still above basal. In contrast, the increase in prolactin secretion, induced by 8-OH-DPAT was not inhibited by any dose of WAY-100635. At the highest dose of WAY-100635 (10 mg/kg, s.c.), basal prolactin levels were markedly elevated (1550%) and administration of 8-OH-DPAT significantly elevated plasma renin concentration. Taken together, these data indicate that: (1) 8-OH-DPAT stimulates oxytocin, ACTH, and corticosterone but not prolactin secretion via activation of 5-HT1A receptors and (2) blockade of 5-HT1A receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT1A receptor mechanisms.
A Vicentic; Q Li; G Battaglia; L D Van de Kar
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmacology     Volume:  346     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-09-16     Completed Date:  1998-09-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  261-6     Citation Subset:  IM    
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
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MeSH Terms
8-Hydroxy-2-(di-n-propylamino)tetralin / antagonists & inhibitors*,  pharmacology
Adrenocorticotropic Hormone / blood
Corticosterone / blood
Dose-Response Relationship, Drug
Hormones / blood*
Oxytocin / blood
Piperazines / pharmacology*
Prolactin / blood
Pyridines / pharmacology*
Rats, Sprague-Dawley
Serotonin Agonists / pharmacology*
Serotonin Antagonists / pharmacology*
Grant Support
Reg. No./Substance:
0/Hormones; 0/Piperazines; 0/Pyridines; 0/Serotonin Agonists; 0/Serotonin Antagonists; 146714-97-8/WAY 100635; 50-22-6/Corticosterone; 50-56-6/Oxytocin; 78950-78-4/8-Hydroxy-2-(di-n-propylamino)tetralin; 9002-60-2/Adrenocorticotropic Hormone; 9002-62-4/Prolactin

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