Angiotensin II desensitization and Ca++ and Na+ fluxes in cultured intestinal smooth muscle cells.

The effects of angiotensin II (ANG) on Na+ and Ca++ fluxes in cultured intestinal smooth muscle cells from the guinea pig ileum were studied and correlated with the contraction and desensitization observed in whole muscles. The effects of ANG were compared with those of acetylcholine (ACh), an agonist that acts at muscarinic receptors in the intestinal smooth muscle and which does not induce desensitization. Both ANG and ACh stimulated 24Na+ influx upon addition to the cells, and this stimulation persisted for at least 30 min. Both agonists also stimulated 45Ca++ uptake but ANG's effect was transient, whereas that of ACh was persistent. Short-term (30 min) treatment with PMA (phorbol-12-myristate-13-acetate) caused a fade of the tonic response of the whole muscle to ANG, and also blocked this hormone's stimulating effect on 45Ca++, but not on 24Na+ influx. Long-term (7 hr) treatment with PMA, which suppresses protein kinase C activity, restored ANG's ability to stimulate 45Ca++ influx. The stimulating effects of ACh on 24Na+ and 45Ca++ influxes were not affected by short- or long-term treatment of the cells with PMA. Our results suggest that ANG desensitization involves protein kinase C inhibition of a step in the stimulus-response chain that is subsequent to phospholipase C-activation.