PROLIFEROGENIC EFFECT OF NEUROTENSIN (NT) AND NEUROMEDIN-N (NMN) ON THE RAT ADRENAL-CORTEX - EVIDENCE THAT ANGIOTENSIN-II MEDIATES THE EFFECT OF NMN, BUT NOT OF NT

NT and NMN, two biologically active peptides acting via the same speci fic receptor, are both able to stimulate in vivo the proliferative act ivity of rat adrenocortical cells. The present study aimed to investig ate whether the mechanism underlying th is effect of NT and NMN may in volve an enhanced production of angiotensin-II (ANG-II), a potent adre nocortical proliferogenic factor. Metaphases per adrenal section were counted 120 min after vincristin injection. A bolus administration of ANG-II resulted in a marked increase in the number of metaphase-arrest ed cells 12, 24 and 48 h after the beginning of the experiment; the co ncomitant administration of saralasin (SAR), a competitive antagonist of ANG-II, completely blocked the proliferogenic effect of ANG-II. NT- evoked rise in the number of meta phases occurred 48 h after administr ation and was not influenced by the simultaneous SAR injection. On the contrary, NMN injection induced a burst of adrenocortical cell prolif eration within 12 h, and this effect was prevented by SAR. These data suggest that ANG-II mediates the proliferogenic effect of NMN, but not that of NT.