Excitatory and inhibitory dopaminergic regulation of oxytocin secretion in the lactating rat: evidence for respective mediation by D-1 and D-2 dopamine receptor subtypes.
The present experiments were designed to test whether the previously reported excitatory and inhibitory effects of dopamine (DA) on the secretion of oxytocin (OT) in lactating rats are exerted at different DA receptor subtypes, and to examine whether one or both of these effects might occur at the level of the posterior pituitary. The basal release of OT in nonsuckled, lactating rats was increased after intravenous administration of the D-1 DA agonist SKF 38393, and this effect, as well as the suckling-induced release of OT, was prevented by treatment with the D-1 DA antagonist SCH 23390, suggesting that DA may exert an important stimulatory influence over OT secretion through an action at the D-1 DA receptor subtype. A small stimulation of basal PRL release was also produced by SKF 38393, but blockade of the D-1 DA receptor did not prevent the suckling-induced release of this hormone. Stimulation of the D-2 DA receptor with PPHT had no effect on basal OT release in nonsuckled rats, but this agent, as well as another D-2 DA agonist, bromocriptine, prevented the suckling-induced release of both OT and PRL. The inhibitory effect of D-2 DA receptor stimulation was blocked by the D-2 DA antagonist domperidone, which increased the basal release of both hormones when given alone. These observations confirm previous findings that inhibitory effects of DA on suckling-induced OT release are mediated through activation of the D-2 DA receptor. To test whether either dopaminergic effect occurs at the level of neurosecretory endings in the neurointermediate lobe (NIL), the stalk-NIL was isolated from lactating rats and perifused in vitro. The stalk-NIL junction was electrically stimulated for 4 s, and the effects of selective D-1 DA and D-2 DA agonists and antagonists on the basal and electrically evoked release of OT and vasopressin (VP) was assessed using the two stimulation (S2/S1) paradigm. Electrical stimulation produced marked increases in release of both neural lobe peptides in a Ca(2+)-dependent manner, and the electrically evoked release of OT, but not VP, was enhanced by the opiate antagonist naltrexone (10 microM). Consistent with the in vivo results, SKF-38393 (20 microM) produced a small, but statistically significant, increase in electrically induced OT release, while SCH 23390 (20 microM) was without significant effect. Neither drug affected the basal release of OT or the basal or electrically stimulated release of VP.(ABSTRACT TRUNCATED AT 400 WORDS)
Crowley
W R
WR
Department of Pharmacology, College of Medicine, University of Tennessee-Memphis.
Parker
S L
SL
Armstrong
W E
WE
Wang
W
W
Grosvenor
C E
CE
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004558:Electric Stimulation; D005260:Female; D007774:Lactation / Q000502:physiology*; D009271:Naltrexone / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014667:Vasopressins / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014667:Vasopressins; D001971:Bromocriptine; D010121:Oxytocin; D004294:Domperidone; D009271:Naltrexone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine