Multiple regulation of adenylyl cyclase activity by G-protein coupled receptors in human foetal lung fibroblasts

The pharmacological profile of adenylyl cyclase activity was analysed in WI -38 human foetal lung fibroblasts. Among various agents that act through G- protein coupled receptors, only the beta -adrenergic agonist isoproterenol stimulated and the tetradecapeptide somatostatin (SRIF, sst) inhibited the enzyme activity. The use of the reverse transcription-polymerase chain reac tion (RT-PCR) methodology with appropriate cDNAs allowed us to identify the expression of four subtypes of SRIF transmembrane receptors (sst1-4 but no t sst5 receptors) in this cell line. By RT-PCR and immunochemistry techniqu es, we also demonstrated the expression of stimulatory (alpha (s)) and inhi bitory (alpha (i1), alpha (i2) and alpha (i3)) G-protein subunits. The know n role of the adenylyl cyclase system in cell proliferation and differentia tion mechanisms together with the present analysis of the corresponding reg ulatory network in fibroblasts of human foetal lung add knowledge on the ce ll line WI-38 that is widely used as a model system in studying cell growth . The importance of this cell class in normal and abnormal lung function an d development reinforces the significance of these results. (C) 2000 Elsevi er Science B.V. All rights reserved.