Interaction between nitric oxide and endocannabinoids on the regulation of oxytocin release

ANDREA DE LAURENTIIS; BERENICE BURDET; JAVIER FERNANDEZ-SOLARI; MARÍA ZORRILLA ZUBILETE; VALERIA RETTORI

Institute for Advanced Studies, of the Hebrew University of Jerusalem

Workshop; Joint Workshop of the Joint Research Conference of the Institute for Advanced Studies and the Israel Science Foundation on "Cannabinoids in Biology and Medicine",; 2010

Institute for Advanced Studies and the Israel Science Foundation

Nitric oxide (NO) synthase (NOS) is expressed in the magnocellular neurons which produce oxytocin (OXT) and its inhibition increases OXT release in vivo. In a previous study in vitro we found that anandamide (AEA) inhibits OXT release from neurohypophysis (NH) and increases its release from hypothalamus (HYP). Therefore, we investigated the participation of NO and cannabinoid receptors (CB1 and CB2) in these effects.   AEA (10-9M) increased (p<0.01) NOS activity in both HYP and NH. Sodium nitroprusside (600µM), a NO donor, decreased (p<0.01) OXT release from HYP and NH. In addition, haemoglobin (40µg/ml), a scavenger of NO, augmented the increase of OXT release induced by AEA in HYP while blocked the decrease induced in NH. The presence of AM251 (10-5M), a CB1 antagonist, completely prevented the stimulatory effect of AEA on OXT release in HYP but did not modify the inhibitory effect of AEA on OXT release from NH. On the contrary, AM630 (10-5M), a CB2 antagonist, reverted the inhibitory effect in NH and was without effect in HYP. The evaluation of CB1 and CB2 mRNA by quantitative RT-PCR showed that both are present in the HYP but in NH there is a higher quantity of CB2 mRNA. Western blot studies yielded higher amount of CB2 protein in NH that was almost undetectable in HYP.   We conclude that the opposite effects of AEA on OXT release between HYP and NH may be due to different intracellular pathways activated by these subtypes of cannabinoid receptors. (Grants: BID PICT 06-0258, CONICET PIP02546).