Reexamination of dopamine as the prolactin-release inhibiting factor (PIF): supplementary agent may be required for dopamine to function as the physiological PIF

Abstract

A large number of studies have been performed concerning dopamine's inhibitory effect on prolactin release, but many of these studies have examined the effect of dopamine dissolved in a solution containing ascorbic acid. Ascorbic acid, routinely used to protect dopamine from oxidation, alone does not stimulate or inhibit prolactin release, but it can potentiate the inhibitory effect of dopamine in a static monolayer culture system by approximately 100 times. We have closely examined the inhibitory effect of dopamine on prolactin release in the absence of ascorbic acid using a perifusion system. Male rat adenohypophyses were dispersed with trypsin and cultured in a Petri dish to form cell clusters. Inhibition of prolactin release by dopamine (1 mumol/L) in the absence of ascorbic acid was sustained for only 63 min during the 2-h perifusion period. Following a 2-h period of incubation of dopamine in the same experimental solution, the dopamine concentration was reduced from 1 to 0.18 mumol/L, yet this "2-h-old dopamine" was still effective in inhibiting prolactin release (approximately 30 min). This result suggests that the lactotrophs may be desensitized by chronic exposure to a high concentration of dopamine in the absence of ascorbic acid. In contrast, when a low concentration of dopamine (3 nmol/L) containing ascorbic acid (0.1 mmol/L) was perifused, inhibition of prolactin release was sustained for the entire 2-h perifusion period. Although there may be a large number of explanations for dopamine's transient inhibitory effect on prolactin release, the present results suggest that dopamine may require supplementary agent(s) to effectively inhibit prolactin release and thus function as the prolactin release inhibitory factor (PIF).(ABSTRACT TRUNCATED AT 250 WORDS)

High Concentrations of Dopamine and Epinephrine Protect Dopaminergic D₂ Receptors from Inactivation by Phenoxybenzamine on Primary Cultured Rat Lactotrophs

“…We understand that the poten tiating effect of ascorbic acid on dopaminergic inhibition of prolactin release is not a simple pharmacological ac tion, but carries physiological relevance, since the physio logical concentration of ascorbic acid in the blood (23-85 pm ol/l) is high enough to potentiate the dopaminergic action [17]. In this study, ascorbic acid is not a simple pharmacological additive to protect dopamine, but simu lates PIF, since dopamine plus ascorbic acid is believed to be the PIF [17].…”

Regulation of prolactin secretion: Dopamine is the prolactin‐release inhibiting factor (PIF), but also plays a role as a releasing factor (PRF)

“…Perifusion of a high concentration of dopamine (1,000 nM) could not sustain inhibitory action on prolactin release during a 2 h perifusion period, but is able to inhibit prolactin release for only 50-60 min in an in vitro perifusion system (Shin et al, 1997). However, when a small amount of ascorbic acid (0.1 mM) is added in a low concentration of dopamine (3 nM) solution, prolactin release was inhibited during an entire 2 h experimental period (Shin et al, 1990a). Dopamine (3nM) in this experiment is substantially lower than the physiological concentrations in the portal blood.…”

“…Ascorbate (0.1 mM) is at a physiological concentration in plasma. This inability to inhibit prolaclin release is not entirely caused by inactivation of dopamine according to following two pieces of evidence: (a) the dopamine half-life is 36 min in DMEM (Shin et al, 1990a) and thus dopamine concentration should not be decreased to less than 1/4 of original concentration during the 60 min perifusion period; 1,000nM dopamine will be decreased to 250 nM during 72 min period, which is higher than 10 times the physiological concentration, (b) 2 h old dopamine stored in the same condition as perifusion medium, was still able to inhibit prolactin release although 1000 nM dopamine can inhibit prolactin release for less than 60 min during perifusion period (Shin et al, 1990a).…”

Somatostatin partially impedes the stimulatory effects of thyrotrophin-releasing hormone and dibutyryl cyclic AMP on prolactin release: prolactin release through multiple routes

“…Dopamine is believed to be the PIF, but it cannot inhibit prolactin release for a long period of time in a perifusion system (Shin, Hanna, Hong & Jhamandas, 1990). Ascorbic acid potentiates the inhibitory effect of dopamine by about 100-fold (Shin & Stirling, 1988) and plasma contains a high concentration (50-150 pmol/1) of ascorbic acid (Scully, 1986).…”