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 (rCgA(1-128)), the first N-terminal cleavage product of rat CgA, is 87% homologous to the bovine vasostatin I (bCgA(1-76)), 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 bCgA(7-40) and bCgA(47-70) with elements of the arterial wall by fluorescence microscopy. Secondly, rCgA(7-57), bCgA(1-40), bCgA(7-40) and bCgA(47-66) (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 (rCgA(7-57)) evoked a significant delay in the onset of forced dilatation at 170 mm Hg, in contrast to the bovine peptides bCgA(1-40), bCgA(7-40) and bCgA(47-66) (chromofungin). Neither Rh-bCgA(7-40) nor Rh-bCgA(47-70) stained the endothelial layer, while Rh-bCgA(47-70) but not Rh-bCgA(7-40) stained the smooth muscle compartment. Analogously, bCgA(47-66) but not bCgA(7-40) reduced intracellular calcium, however without modifying the myogenic response. Thus, the betagranin peptide rCgA(7-57) and the two bovine chromofungin-containing peptides, highly homologous to the corresponding sequence (rCgA(47-66)), affected the rat cerebral artery without vasodilator effects, indicating significant species differences in vasoactivity of the N-terminal domain of CgA.
Mandalà
Maurizio
M
Department of Biomedicine, Division of Physiology, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
Brekke
Johan Fredrik
JF
Serck-Hanssen
Guldborg
G
Metz-Boutigue
Marie-Hélène
MH
Helle
Karen B
KB
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D020769:Posterior Cerebral Artery / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011921:Rats, Inbred WKY
D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C506153:chromogranin A, rat; D002118:Calcium