Effects of delta9-THC on VIP-induced prolactin secretion in anterior pituitary cultures: evidence for the presence of functional cannabinoid CB1 receptors in pituitary cells.
Peripheral administration of cannabinoid CB1 receptor agonists to laboratory rats induce a brief rise in plasma prolactin (PRL) levels followed by a prolonged decrease in PRL secretion from the pituitary. While the inhibitory component of this biphasic response depends on the cannabinoid-induced activation of dopamine release from hypothalamic terminals located in the median eminence, the neurobiological mechanisms underlying the activation phase of PRL release remains to be explained. In the present study the possible direct effect of the cannabinoid receptor agonist delta9-Tetrahydrocannabinol (THC) on prolactin secretion and cAMP accumulation was examined in anterior pituitary cultures. THC (0.1 and 1 microM) increased cAMP levels, and induced PRL release (1 and 10 mu). THC did not affect vasoactive intestinal peptide (VIP, 0.5 microM) induced cAMP accumulation in pituitary cultures, showing additive effects at THC 1 microM concentration. However, THC did prevent VIP-dependent increases in prolactin secretion. These results indicate that THC, through a direct pituitary action, activates both the synthesis of cAMP and PRL release and interferes with intracellular mechanisms involved in PRL secretion by VIP. These actions could be mediated through cannabinoid CB1 receptors which were found to be present in anterior pituitary cells, including lactotrophs, as revealed by immunocytochemistry with a specific polyclonal antibody raised against the CB1 receptor protein.
Rodríguez de Fonseca
F
F
Instituto Complutense de Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense, Madrid, Spain. pspsc10@sis.ucm.es
Wenger
T
T
Navarro
M
M
Murphy
L L
LL
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000032:analysis / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014660:Vasoactive Intestinal Peptide; D013759:Dronabinol; D011388:Prolactin; D000242:Cyclic AMP