Evidence for the involvement of histaminergic neurones in the regulation of the rat oxytocinergic system during pregnancy and parturition.
1. Previous studies have shown that histaminergic neurones of the tuberomammillary nucleus project directly to hypothalamic magnocellular nuclei and that intracerebroventricular administration of histamine increases the synthetic activity of magnocellular oxytocin neurones. 2. Histaminergic neurones of the dorsomedial tuberomammillary nucleus that project to the magnocellular region of the paraventricular nucleus are activated during late pregnancy and lactation, as measured by an increase in mRNA for the synthetic enzyme histidine decarboxylase. 3. There is a concomitant increase in oxytocin mRNA in magnocellular neurones of the paraventricular nucleus. This increase in mRNA contributes to an accumulation of oxytocin before birth and to continued oxytocin synthesis during lactation. 4. Intracerebroventricular administration of mepyramine, a specific antagonist of the H1 histamine receptor, causes a delay in the birth of subsequent pups if given to the mother during parturition. Vehicle or the H2 receptor antagonist cimetidine has no effect. Thus, histamine acts centrally, via H1 receptors, during parturition and may have an excitatory effect on oxytocin release. 5. These results suggest that afferent histaminergic neurones show increased activity during pregnancy and may be responsible for the increase of synthesis in magnocellular oxytocin neurones at this time. If, as previously reported, these histamine neurones can reduce the electrical activity of oxytocin neurones via H2 receptors, then they may have a dual effect, increasing the synthesis of oxytocin while inhibiting its premature release. At term, any inhibitory effects of histamine are overcome to allow oxytocin secretion.
Luckman
S M
SM
Department of Neurobiology, Babraham Institute, Cambridge, UK. simon.luckman@bbsrc.ac.uk
Larsen
P J
PJ
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics; D017403:In Situ Hybridization; D007743:Labor, Obstetric / Q000187:drug effects / Q000502:physiology*; D007774:Lactation / Q000502:physiology; D008326:Mammillary Bodies / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D011738:Pyrilamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D006633:Histamine Antagonists; D012333:RNA, Messenger; D010121:Oxytocin; D002927:Cimetidine; D006632:Histamine; D006640:Histidine Decarboxylase; D011738:Pyrilamine