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)
Horváth
G
G
Heim Pál Pediatric Hospital, Budapest, Hungary.
Gyévai
A
A
Rappay
G
G
Makara
G B
GB
Nagy
I
I
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D002121:Calcium Channel Blockers; C076129:N-benzyloxycarbonyl-phenylalanyl-leucyl-phenylalaninal; C076130:N-benzyloxycarbonyl-phenylalanylleucyl-prolinal; D009842:Oligopeptides; D013973:Thyrotropin-Releasing Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C060811:butyloxycarbonyl-glutaminyl-leucyl-lysinal; D011188:Potassium; D002118:Calcium