A mechanism additional to cyclic AMP accumulation for vasoactive intestinal peptide-induced prolactin release.
Vasoactive intestinal peptide (VIP) is a prolactin (PRL)-releasing factor which has been proposed to exert its secreting property by activating the adenylate cyclase enzyme. The present study shows that the omission of external Ca2+ did not affect the ability of VIP to induce PRL release while it completely abolished the VIP stimulatory effect on adenylate cyclase. We found that VIP (500 nM) stimulated PRL secretion in a time-dependent manner reaching a plateau at 3 min. This pattern was not changed when Ca2+ was omitted from the incubation medium. When tested at different concentrations, VIP stimulated PRL release with EC50 values of 1.3 nM in the presence of Ca2+ and 30 nM in the absence of Ca2+. On the other hand, Ca2+ removal completely suppressed the VIP-induced cAMP formation. VIP (200 nM) was also found to activate Ca2+ influx into pituitary cells. The increase in Ca2+ permeability showed a peak at 5 s and remained significantly higher than control values until 1 min. In conclusion, in an experimental condition where Ca2+ was omitted from the medium, VIP was found to induce PRL release without stimulating cAMP production. This cAMP-independent PRL release was blocked by preincubation of the cells with 1 microgram/ml pertussis toxin. An additional mechanism other than adenylate cyclase activation or Ca2+ entry is proposed to sustain VIP-induced PRL release.
Pizzi
M
M
Institute of Pharmacology and Experimental Therapeutics, School of Medicine, Brescia University, Italy.
Memo
M
M
Benarese
M
M
Simonazzi
E
E
Missale
C
C
Spano
P F
PF
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D037342:Pertussis Toxin; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D002021:Buffers; D010566:Virulence Factors, Bordetella; D014660:Vasoactive Intestinal Peptide; D011388:Prolactin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D002118:Calcium