WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion

Aleksandra Vicentic, Qian Li, George Battaglia, Louis D. Van de Kar

Research output: Contribution to journalArticle

Abstract

Previous studies suggest that the 5-HT(1A) 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-HT(1A) receptor antagonists made it difficult to confirm that 5-HT(1A) receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT(1A) receptor antagonist, N-[2-[4-(2- methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT(1A) receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 μg/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-HT(1A) receptors and (2) blockade of 5-HT(1A) receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT(1A) receptor mechanisms.

Original languageEnglish (US)
Pages (from-to)261-266
Number of pages6
JournalEuropean Journal of Pharmacology
Volume346
Issue number2-3
DOIs
StatePublished - Apr 10 1998
Externally publishedYes

Fingerprint

8-Hydroxy-2-(di-n-propylamino)tetralin
Oxytocin
Corticosterone
Prolactin
Adrenocorticotropic Hormone
Receptor, Serotonin, 5-HT1A
Renin
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
hydroxide ion

Keywords

  • (Antagonist)
  • 5-HT (5-hydroxytryptamine, serotonin)
  • 5-HT(1A), receptor
  • Hormone
  • Hypothalamus
  • Neuroendocrine
  • Receptor reserve

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion. / Vicentic, Aleksandra; Li, Qian; Battaglia, George; Van de Kar, Louis D.

In: European Journal of Pharmacology, Vol. 346, No. 2-3, 10.04.1998, p. 261-266.

Research output: Contribution to journalArticle

Vicentic, Aleksandra ; Li, Qian ; Battaglia, George ; Van de Kar, Louis D. / WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion. In: European Journal of Pharmacology. 1998 ; Vol. 346, No. 2-3. pp. 261-266.
@article{dd8ba627b3ad43e99d0e653c44edf91d,
title = "WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion",
abstract = "Previous studies suggest that the 5-HT(1A) 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-HT(1A) receptor antagonists made it difficult to confirm that 5-HT(1A) receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT(1A) receptor antagonist, N-[2-[4-(2- methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT(1A) receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 μg/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-HT(1A) receptors and (2) blockade of 5-HT(1A) receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT(1A) receptor mechanisms.",
keywords = "(Antagonist), 5-HT (5-hydroxytryptamine, serotonin), 5-HT(1A), receptor, Hormone, Hypothalamus, Neuroendocrine, Receptor reserve",
author = "Aleksandra Vicentic and Qian Li and George Battaglia and {Van de Kar}, {Louis D.}",
year = "1998",
month = "4",
day = "10",
doi = "10.1016/S0014-2999(97)01607-5",
language = "English (US)",
volume = "346",
pages = "261--266",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion

AU - Vicentic, Aleksandra

AU - Li, Qian

AU - Battaglia, George

AU - Van de Kar, Louis D.

PY - 1998/4/10

Y1 - 1998/4/10

N2 - Previous studies suggest that the 5-HT(1A) 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-HT(1A) receptor antagonists made it difficult to confirm that 5-HT(1A) receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT(1A) receptor antagonist, N-[2-[4-(2- methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT(1A) receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 μg/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-HT(1A) receptors and (2) blockade of 5-HT(1A) receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT(1A) receptor mechanisms.

AB - Previous studies suggest that the 5-HT(1A) 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-HT(1A) receptor antagonists made it difficult to confirm that 5-HT(1A) receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT(1A) receptor antagonist, N-[2-[4-(2- methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT(1A) receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 μg/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-HT(1A) receptors and (2) blockade of 5-HT(1A) receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT(1A) receptor mechanisms.

KW - (Antagonist)

KW - 5-HT (5-hydroxytryptamine, serotonin)

KW - 5-HT(1A), receptor

KW - Hormone

KW - Hypothalamus

KW - Neuroendocrine

KW - Receptor reserve

UR - http://www.scopus.com/inward/record.url?scp=0032502640&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032502640&partnerID=8YFLogxK

U2 - 10.1016/S0014-2999(97)01607-5

DO - 10.1016/S0014-2999(97)01607-5

M3 - Article

C2 - 9652368

AN - SCOPUS:0032502640

VL - 346

SP - 261

EP - 266

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2-3

ER -