A comparison of the concentration-dependent actions of thyrotropin-releasing hormone, angiotensin II, bradykinin, and Lys-bradykinin on cytosolic free calcium dynamics in rat anterior pituitary cells: selective effects of dopamine.

ABSTRACT

Using Indo-1 as a fluorescent probe, we studied the dynamics and the underlying mechanisms of the response of cytosolic free calcium ([Ca2+]i) to different concentrations of four prolactin secretagogues, thyrotropin-releasing hormone, angiotensin II, bradykinin, and lys-bradykinin in rat anterior pituitary cells. Low concentrations (1-100 pM) of these peptides caused a sustained increase in [Ca2+]i, whereas high concentrations (up to 100 nM) caused a large transient elevation of [Ca2+]i that was followed by a lower sustained plateau. Experiments with protein kinase C-depleted cells suggested that phorbol diester-sensitive protein kinase C was not involved in the transition of [Ca2+]i from spike to plateau seen with high concentrations of secretagogue. Specific concentrations of secretagogue mobilized different pools of [Ca2+]i, as indicated by experiments with Ca2(+)-depleted medium. Low concentrations of secretagogue induced a Ca2+ response that was abolished by Ca2(+)-depleted medium, whereas high concentrations generated a [Ca2+]i response that was refractory to Ca2(+)-depleted medium. Dopamine (100 nM) abolished the [Ca2+]i plateau response to all four agents at low concentrations and selectively reduced the plateau component of the responses elicited at high concentrations of secretagogue. If the plateau component is represented by utilization of either extracellular Ca2+ or a cell-associated EGTA-accessible pool(s) of Ca2+, then dopamine modulates one or both of these calcium sources.