Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin.
Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 +/- 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 +/- 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 +/- 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.
Russell
S H
SH
ICSM, Endocrine Unit, Hammersmith Hospital, Du Cane Road, London, UK.
Kim
M S
MS
Small
C J
CJ
Abbott
C R
CR
Morgan
D G
DG
Taheri
S
S
Murphy
K G
KG
Todd
J F
JF
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004294:Domperidone / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009496:Neurotensin / Q000378:metabolism; D064446:Orexin Receptors; D000068797:Orexins; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D013004:Somatostatin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D002352:Carrier Proteins; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; D013004:Somatostatin; D004294:Domperidone; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D003346:Corticotropin-Releasing Hormone