Recent developments in the techniques of molecular biology and the availability of inhibitors of the renin-angiotensin system have provided new insight into renin-angiotensin research. The control mechanism of renin release and the metabolism of circulating renin have been well characterized on the molecular level. Angiotensin II has been shown to play an important role not only in the regulation of blood pressure but also in cell growth and hypertrophy. ACE inhibitors are effective for the treatments of hypertension and heart failure. Furthermore, recent studies suggest that ACE inhibitors may prevent atherosclerosis and glomerulosclerosis. Angiotensin II receptor antagonists have similar beneficial effects. These effects of ACE inhibitors and angiotensin 11-receptor antagonists may be mediated by growth factors and the extracellular matrix.
Synaptic plasticity, a physiological basis of learning and memory, is mainly classified into two categories: 1) relatively short-term changes in electrical activities and 2) more long-lasting morphological changes in synapses. Studies on neuronal differentiation have provided detailed clarification of many of the morphological changes in synapses. Although it has been demonstrated that neuronal differentiation is induced by a variety of stimuli, the mechanism of neuronal differentiation has never been sequentially understood. Since there must be unknown factors relevant to these complicated processes, it is important to find and identify the novel intracellular factors that are able to induce the differentiation of neurons. Differential screening is useful cloning method to identify molecules without any information about their structures. Genes expressed in a distinct pattern among two or more groups, eg. different drug-treated cells, tissues and so on, can be isolated. To identify novel neuronal differentiation factors, we differentially screened approximately 500, 000 primary clones from the cDNA library of NG108-15 cells treated with TPA and diBu-cAMP for 72 hr. Using two single strand cDNA probes, which were reverse-transcribed from poly(A)+RNA, TA-20 was isolated from cells treated with TPA and diBu-cAMP (probe TA) or from cells treated with diBu-cAMP alone (probe A) for 72 hr. Clones that hybridized preferentially to the probe TA were further investigated by Southern and Northern blots. Thus the identified clone TA20 is a novel gene and plays functional roles as a neuronal differentiation factor.