Melatonin receptors in benign prostate epithelial cells: evidence for the involvement of cholera and pertussis toxins-sensitive G proteins in their signal transduction pathways.
BACKGROUND
Melatonin, the hormone secreted nocturnally by the pineal gland, binds to epithelial cells from the human benign prostate, and can reduce their growth and viability. The possible involvement of GTP binding proteins cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in melatonin responses in these cells were investigated.


METHODS
The effects of melatonin on cAMP and cGMP were assessed in prostate cells untreated or pretreated with pertussis toxin (PTX) or cholera toxin (CTX).


RESULTS
Melatonin augmented cAMP but reduced cGMP in the epithelial cells (maximal responses at 10 nM). The increase in cAMP was attenuated by PTX, but not by CTX, whereas the decrease in cGMP was attenuated by CTX, but not by PTX. CTX, but not PTX, abolished the melatonin-mediated suppression of 3H-thymidine incorporation. In addition, melatonin facilitated the CTX- and PTX-mediated ADP ribosylation of 44- and 41-kilodalton proteins, respectively. The cGMP analogue 8-bromo-cGMP, negated the melatonin-mediated decrease in 3H-thymidine incorporation, whereas H89, a protein kinase A inhibitor, did not inhibit melatonin's effect.


CONCLUSIONS
Melatonin receptors in the human benign prostate epithelial cells enhance cAMP and inhibit cGMP through PTX- and CTX-sensitive G proteins, respectively. The decrease in DNA synthesis may be secondary to the melatonin-mediated decrease in cGMP.
Gilad
E
E
Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Pick
E
E
Matzkin
H
H
Zisapel
N
N
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D008875:Middle Aged; D037342:Pertussis Toxin; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D044094:Receptors, Melatonin; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; C016276:8-bromocyclic GMP; D004247:DNA; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D008550:Melatonin