The Dynamics of Arachidonic Acid Liberation and Prolactin Release: A Comparison of Thyrotropin-Releasing Hormone, Angiotensin II, and Neurotensin Stimulation in Perifused Rat Anterior Pituitary Cells*

Abstract

The dynamics of arachidonic acid (AA) liberation and PRL release were highly correlated in perifused rat anterior pituitary cells during stimulation by three different neuropeptides: TRH, angiotensin II (AII), and neurotensin (NT). After preincubation of these cells with 1 microCi [3H]AA, a 20-min perifusion with AII (100 nM), TRH (100 nM), or NT (1 microM) elicited a sharp initial increase in PRL release and [3H]AA efflux, which rapidly subsided (within 6 min) to less elevated levels of PRL release and AA liberation. The plateau responses were sustained throughout the remainder of the 20-min treatment period; after the cessation of neuropeptide perifusion, the responses rapidly returned to basal levels. AII and TRH elicited a greater initial stimulation of PRL release and AA liberation, whereas NT resulted in less pronounced initial responses and a greater plateau of sustained PRL release and AA liberation. Dopamine (DA; 500 nM) or calcium-depleted medium (containing 60 microM EGTA) evenly attenuated the stimulation of PRL release throughout exposure to the neuropeptides; however, the initial stimulation of AA efflux by AII and TRH was relatively resistant to inhibition by DA or calcium-depleted medium. In contrast, the stimulation of AA liberation by NT was abolished by DA or calcium-dependent medium. These results establish that the time course of AA liberation is complimentary to that of PRL release during stimulation by AII, TRH, and NT and support a possible role for AA liberation and metabolism as one of the mechanisms that participates in the regulation of PRL release. A lesser ability of NT to elicit functional and biochemical responses to intracellular calcium mobilization is postulated as an explanation for the observed differences among AII, TRH, and NT effects on PRL release and AA liberation.