The Inhibition of Phosphatidylinositol Turnover: A Possible Postreceptor Mechanism for the Prolactin Secretion-Inhibiting Effect of Dopamine^*

Abstract

We studied the association between the inhibition of phosphatidylinositol (PI) turnover and the inhibition of PRL secretion in the presence of dopamine. The incorporation of radiolabeled phosphate into anterior pituitary gland PI as well as serum PRL levels were significantly (P less than 0.01) greater in female than in male rats. No significant sex-related difference was found in the incorporation by pituitary tissue of 32P into phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Dopamine decreased the incorporation of 32P into PI, but not into PC or PE, by female rat pituitary glands; this effect was reversed by two dopamine receptor-blocking agents, haloperidol and pimozide. After dopamine was removed from the incubation medium, basal 32P incorporation into PI was restored within 10 min. The administration of bromocriptine (500 micrograms/kg, ip, 4 h earlier) significantly reduced pituitary PI turnover. Conversely, in vivo injection of alpha-methyl-p-tyrosine (alpha MpT; 200 mg, ip, 2.5 h before death), an inhibitor of catecholamine biosynthesis, dramatically increased serum PRL levels. In vitro incorporation of 32P into PI, but not into PC or PE, increased (+130%) when these glands were incubated for 30 min with radiolabeled phosphate. The in vitro addition of 0.5 microM dopamine to glands from alpha MpT-treated rats counteracted the stimulation of 32P incorporation into PI produced by alph MpT treatment. In rats bearing the transplantable PRL-secreting tumor MtTW15, the hyperprolactinemia produced by the tumor stimulates hypothalamic turnover of dopamine, with a consequent inhibition of pituitary gland PRL secretion. 32P incorporation into PI, but not into PC or PE, was significantly (P less than 0.01) inhibited (-41%) in pituitary glands from these rats. The injection of alpha MpT (200 mg/kg, ip) or haloperidol (2 mg/kg, ip) 12 and 3 h before death into MtTW15 tumor-bearing rats abolished the inhibition of 32P incorporation into pituitary PI. Dopamine also decreased PI turnover in the 7315a PRL-secreting pituitary tumor. Our data indicate that the PI cycle may be an intracellular mechanism controlling PRL release in the rat and that the changes in its cleavage and turnover may be an early postreceptor event responsible for the inhibition of PRL secretion produced by factors such as dopamine.

A subtype of opioid κ‐receptor is coupled to inhibition of Gil‐mediated phospholipase C activity in the guinea pig cerebellum

“…The receptor-mediated inhibition of PLC as a phenomena was first reported by Canonico et al [12] for the D2 receptor in pituitary and followed up by several groups [13]. Most recently, we also found that the x-opioid agonist inhibited the GTP-stimulated PLC activity in synaptic membranes of the guinea pig cerebellum [14].…”

Mechanism of dopamine mediated inhibition of neuropeptide Y release from pheochromocytoma cells (PC12 cells)

“…In a number of systems it is well established that activation of D 2 receptor results in multiple signaling mechanisms including inhibition of adenylate cyclase [46][47], inhibition of phosphoinositide turnover [48][49][50], and activation of potassium channels [51]. We further investigated the potential signaling mechanisms involved in the dopamine mediated inhibition of NPY-ir release.…”

Dopamine Inhibits the Arachidonate and Prolactin Release Stimulated by Thyrotropin-Releasing Hormone through an Islet-Activating Protein-Sensitive GTP-Binding Protein in Anterior Pituitary Cells

“…In additional experi ments, the labeling of cellular phospholipids with [3H]-AA was deter mined by incubating the cultured cells for 90 min with [3H]-AA (0.25 gC i/m l) and then extracting and isolating the phospholipids as de scribed previously [8].…”