Physiological characterization of two functional states in subpopulations of prolactin cells from lactating rats.

Lledo, Pierre−Marie; Guérineau, Nathalie C.; Mollard, Patrice; Vincent, J.D.; Israël, Jean-Marc

doi:10.1113/jphysiol.1991.sp018607

Cited by 47 publications

(22 citation statements)

References 41 publications

(61 reference statements)

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“…3), the reduced prolactin release elicited by hypotonic stimulation vs. KCl depolarization (Fig. 2) is likely due to the reduced discharge of hormone per cell rather than due to response of a smaller, distinct fraction of cells in a heterogeneous population of lactotrophs (29).…”

Section: Discussionmentioning

confidence: 89%

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Hypotonicity and peptide discharge from a single vesicle

Jorgačevski¹,

Stenovec²,

Kreft³

et al. 2008

American Journal of Physiology-Cell Physiology

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crine secretory vesicles discharge their cargo in response to a stimulus, but the nature of this event is poorly understood. We studied the release of the pituitary hormone prolactin by hypotonicity, because this hormone also contributes to osmoregulation. In perfused rat lactotrophs, hypotonicity resulted in a transient increase followed by a sustained depression of prolactin release, as monitored by radioimmunoassay. In single cells imaged by confocal microscopy, hypotonicity elicited discharge of the fluorescently labeled atrial natriuretic peptide cargo from ϳ2% of vesicles/cell. In contrast, KCl-induced depolarization resulted in a response of ϳ10% of vesicles/cell, with different unloading/loading time course of the two fluorescent probes. In cell-attached studies, discrete changes in membrane capacitance were recorded in both unstimulated and stimulated conditions, reflecting single vesicle fusion/fissions with the plasma membrane. In stimulated cells, the probability of occurrence of full fusion events was low and unchanged, whereas over 95% of fusion events were transient, with the open fusion pore probability, the average pore dwell-time, the frequency of occurrence, and the fusion pore conductance increased. Hypotonicity only rarely elicited new fusion events in silent membrane patches. The results indicate that, in hypotonicitystimulated lactotrophs, transient vesicle fusion mediates hormone release.prolactin; hormone secretion; rat lactotrophs; fusion pore; postfusion release regulation AMONG ITS MANY FUNCTIONS, peptidergic hormone prolactin plays also a role in osmoregulation (14). Previous studies demonstrated prolactin release from isolated tissue (18,34,41,42) or cells in response to hyposmotic stimulation (41, 50), which required extracellular calcium (23,40,41). While these findings suggest that prolactin is likely released by exocytosis in response to hyposmotic stress, secretory activity at the single vesicle level in response to hypotonicity was not monitored directly yet. In particular, it is unclear whether the hormone is released rapidly after complete collapse of vesicles into the plasma membrane (24) by full fusion exocytosis (21) or by kiss-and-run exocytosis (1, 13), whereby vesicles transiently fuse with the plasma membrane, forming a channel with the extracellular space, termed the fusion pore.To address these questions, we studied rat pituitary lactotrophs, which release prolactin stored in a highly aggregated form in large dense-core secretory vesicles (10). To monitor secretory activity, we used perfusion experiments and radioimmunoassays and recorded single exocytotic and vesicle release events in real time, using confocal microscopy, styryl dyes, and fluorescently labeled peptides (2, 45). To directly study fusion pore properties, we used electrophysiological methods to monitor membrane capacitance (C m ), which is linearly related to changes in membrane area (30,35,48,53). Experimental evidence indicates that fusion of secretory vesicles in lactotrophs occurs spontaneously an...

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Section: Discussionmentioning

confidence: 89%

“…Since the density of cells was similar under both conditions, the reduced amount of hormone release after hypotonic stimulation may reflect reduced release of prolactin per cell. However, it cannot be entirely excluded that lactotrophs are functionally heterogeneous cells (29) and may thus exhibit distinct sensitivity to the two stimuli.…”

Section: Discussionmentioning

confidence: 99%

Hypotonicity and peptide discharge from a single vesicle

Jorgačevski¹,

Stenovec²,

Kreft³

et al. 2008

American Journal of Physiology-Cell Physiology

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“…It has been proposed previously that lactotroph heterogeneity was due to differential expression of sodium or calcium channels (Horta et al, 1991;Lledo et al, 1991). These differences in expression of the inward currents would separate lactotrophs into active and silent sub-populations.…”

Section: Assumptions and Experimental Testsmentioning

confidence: 99%

Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents

et al. 2006

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Dopamine (DA) released from the hypothalamus tonically inhibits pituitary lactotrophs. DA (at micromolar concentration) opens potassium channels, hyperpolarizing the lactotrophs and thus preventing the calcium influx that triggers prolactin hormone release. Surprisingly, at concentrations 1000 lower, DA can stimulate prolactin secretion. Here, we investigated whether an increase in a K + current could mediate this stimulatory effect. We considered the fast K + currents flowing through large-conductance BK channels and through A-type channels. We developed a minimal lactotroph model to investigate the effects of these two currents. Both I BK and I A could transform the electrical pattern of activity from spiking to bursting, but through distinct mechanisms. I BK always increased the intracellular Ca 2+ concentration, while I A could either increase or decrease it. Thus, the stimulatory effects of DA could be mediated by a fast K + conductance which converts tonically spiking cells to bursters. In addition, the study illustrates that a heterogeneous distribution of fast K + conductances could cause heterogeneous lactotroph firing patterns.

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“…In our view, neurotransmitterlike factors found in LDCV (e.g. dopamine in somatotrophs and lactotrophs) (19) could represent putative candidates since their fast and evanescent actions on pituitary cells (46) could provide a fine tuning of nearby cell activities.…”

Section: Synchronized Ca 2ϩ Transients In the Anterior Pituitarymentioning

confidence: 99%