Chromogranin A-derived peptides: interaction with the rat posterior cerebral artery

Chromogranin A (CgA), an acidic granule protein of the regulated secretory pathway in the diffuse neuroendocrine system, is postulated to serve as a prohormone for regulatory peptides. Betagranin (rCgA1-128), the first N-terminal cleavage product of rat CgA, is 87% homologous to the bovine vasostatin I (bCgA1-76), previously shown to be vasoinhibitory in bovine resistance arteries. In this study the vasoactivity of homologous rat and bovine peptides was investigated in the rat posterior cerebral artery. Firstly, we examined the interaction of rhodamine (Rh)-labelled bCgA7-40 and bCgA47-70 with elements of the arterial wall by fluorescence microscopy. Secondly, rCgA7-57, bCgA1-40, bCgA7-40 and bCgA47-66 (chromofungin) were studied for effects on arterial tone and intracellular calcium as function of pressure in an arteriograph. Although without dilator or constrictor responses at 60-150 mm Hg, the rat peptide (rCgA7-57) evoked a significant delay in the onset of forced dilatation at 170 mm Hg, in contrast to the bovine peptides bCgA1-40, bCgA7-40 and bCgA47-66 (chromofungin). Neither Rh-bCgA7-40 nor Rh-bCgA47-70 stained the endothelial layer, while Rh-bCgA47-70 but not Rh-bCgA7-40 stained the smooth muscle compartment. Analogously, bCgA47-66 but not bCgA7-40 reduced intracellular calcium, however without modifying the myogenic response. Thus, the betagranin peptide rCgA7-57 and the two bovine chromofungin-containing peptides, highly homologous to the corresponding sequence (rCgA47-66), affected the rat cerebral artery without vasodilator effects, indicating significant species differences in vasoactivity of the N-terminal domain of CgA.