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 reaction (RT-PCR) methodology with appropriate cDNAs allowed us to identify the expression of four subtypes of SRIF transmembrane receptors (sst1-4 but not sst5 receptors) in this cell line. By RT-PCR and immunochemistry techniques, we also demonstrated the expression of stimulatory (alpha (s)) and inhibitory (alpha (i1), alpha (i2) and alpha (i3)) G-protein subunits. The known role of the adenylyl cyclase system in cell proliferation and differentiation mechanisms together with the present analysis of the corresponding regulatory network in fibroblasts of human foetal lung add knowledge on the cell 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 and development reinforces the significance of these results. (C) 2000 Elsevier Science B.V. All rights reserved.