Gene expression profiling of rat brain neurons reveals angiotensin II-induced regulation of calmodulin and synapsin I: Possible role in neuromodulation

Angiotensin (Ang II) activates neuronal AT, receptors located in the hypoth alamus and the brainstem and stimulates noradrenergic neurons that are invo lved in the control of blood pressure and fluid intake. In this study we us ed complementary DNA microarrays for high throughput gene expression profil ing to reveal unique genes that are linked to the neuromodulatory actions o f Ang II in neuronal cultures from newborn rat hypothalamus and brainstem. Of several genes that were regulated, we focused on calmodulin and synapsin I. Ang II(100 nM; 1-24 h) elicited respective increases and decreases in t he levels of calmodulin and synapsin I messenger RNAs, effects mediated by AT(1) receptors. This was associated with similar changes in calmodulin and synapsin protein expression. The actions of Ang II on calmodulin expressio n involve an intracellular pathway that includes activation of phospholipas e C, increased intracellular calcium, and stimulation of protein kinase C. Taken together with studies that link calmodulin and synapsin I to axonal t ransport and exocytotic processes, the data suggest that Ang II regulates t hese two proteins via a Ca2+-dependent pathway, and that this may contribut e to longer term or slower neuromodulatory actions of this peptide.