Influence of oligopeptide aldehydes on intracellular Ca2+ concentration in rat pituitary cells

We investigated the effects of some synthetic tripeptide aldehydes, earlier shown to influence pituitary hormone secretion and 45Ca2+ uptake, on the intracellular free Ca2+ concentration ([Ca2+]i) of rat anterior pituitary cells in suspension. Boc-D-Phe-Leu-Phenylalaninal or Boc-D-Phe-Leu-Prolinal in the tested range of 1-100 or 200 microM, respectively, were ineffective in influencing basal [Ca2+]i but caused a concentration-dependent inhibition in K+ (25 mM)-induced [Ca2+]i elevation. The IC50 of both effects was about 50 microM. In contrast, they did not interfere with the stimulation caused by the calcium channel agonist BAY K 8644 and were also ineffective in influencing the receptor-mediated stimulus of thyrotropin-releasing hormone on [Ca2+]i. On the basis of the present and foregoing results the possible involvement of calcium channels is discussed, but different mechanisms mediating the tripeptide aldehyde inhibition are also considered. A third tripeptide aldehyde, Boc-Gln-Leu-Lysinal (Boc-GLL), showed ionophore-like properties. This nontoxic substance caused a dose-dependent rise up to 400% (at 100 microM) in [Ca2+]i. Its effect is not mediated by voltage-dependent calcium channels, as it cannot be inhibited either by the classical calcium channel antagonists verapamil and nifedipine, or by the above-mentioned inhibitory tripeptide aldehydes. When we decreased the extracellular Ca2+ concentration by the addition of 4 mM EGTA, the effect was inverted and Boc-GLL caused a large fall in [Ca2+]i. We suggest that Boc-GLL may open cell membrane pores through which Ca2+ moves along the concentration gradient.(ABSTRACT TRUNCATED AT 250 WORDS)