Pancreastatin, a chromogranin A-derived peptide, activates Galpha(16) and phospholipase C-beta(2) by interacting with specific receptors in rat heart membranes.
Pancreastatin (PST) is one of the chromogranin A (CGA)-derived peptides with known biological activity. It has a general inhibitory effect on secretion in many exocrine and endocrine systems including the heart atrium. Besides, a role of PST as a counter-regulatory peptide of insulin action has been proposed in the light of its effects on glucose and lipid metabolism in the liver and adipose tissue, where receptors and signaling have been described. Galpha(q/11) pathway seems to mediate PST action. Since PST has been shown to function as a typical calcium-dependent hormone, and increased plasma levels have been found in essential hypertension correlating with catecholamines, we sought to study its possible interaction and signaling in heart membranes. Here, we are characterizing specific PST binding sites and signaling in rat heart membranes. We have found that PST receptor has a K(d) of 0.5 nM and a B(max) of 34 fmol/mg of protein. The PST binding is inhibited by guanine nucleotides, suggesting the functional coupling of the receptor with GTP binding proteins (G proteins). Moreover, PST dose-dependently increases GTP binding to rat heart membranes. Finally, we have studied PST signaling-effector system by measuring phospholipase C (PLC) activity using blocking antibodies against different G proteins and PLC isoforms. We have found that PST stimulates PLCbeta(2)>PLCbeta(1)>PLCbeta(3) by activating Galpha(16) in rat heart membranes. These data suggest that PST may modulate the cardiac function.
González-Yanes
C
C
Department of Medical Biochemistry and Molecular Biology, School of Medicine, University Hospital Virgen Macarena, Av. Sanchez Pizjuan 4, 41009, Seville, Spain.
Santos-Alvarez
J
J
Sánchez-Margalet
V
V
D000818:Animals; D021961:Cell Membrane Structures / Q000378:metabolism; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010187:Pancreatic Hormones / Q000819:agonists / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000737:chemistry / Q000378:metabolism*
D053379:Chromogranin A; D002864:Chromogranins; D010187:Pancreatic Hormones; C506153:chromogranin A, rat; C050836:pancreastatin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins