Role of Ca2+ in the vascular contraction caused by a thrombin receptor activating peptide

• Published in: European journal of pharmacology Vol. 256; no. 1; pp. 37 - 44
• Main Authors: ANTONACCIO, M. J, NORMANDIN, D
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 11.04.1994
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Amino Acid Sequence; Animals; Aorta, Thoracic - drug effects; Biological and medical sciences; Blood vessels and receptors; Calcium - physiology; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Male; Molecular Sequence Data; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Nifedipine - pharmacology; Norepinephrine - pharmacology; Peptide Fragments - pharmacology; Phenylephrine - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha - drug effects; Receptors, Thrombin - drug effects; Vertebrates: cardiovascular system; Serine endopeptidases; Calcium; Rat; Enzyme; Thrombin receptor activating peptide; Rodentia; Smooth muscle; Thrombin; Muscle contraction; Endothelium; Vertebrata; Mammalia; Blood vessel; Hydrolases; Aorta; Circulatory system; Proteinases; Biological receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(94)90613-0

Thrombin receptor activating peptide (TRAP) caused a slowly developing, sustained contraction of endothelium denuded rat aortic rings. Both nifedipine (10 microM) and removal of Ca2+ from the physiological salt solution (PSS) caused significant (60-75%) reductions in the contractile response to TRAP. In Ca(2+)-free PSS the response to both phenylephrine and TRAP were markedly reduced. Readministration of Ca2+ quickly restored the full response to phenylephrine. In contrast, readministration of Ca2+ only partially restored the TRAP response. Depletion of TRAP-sensitive intracellular Ca2+ stores had no effect on the phenylephrine response in Ca(2+)-free PSS. A threshold contracting concentration of TRAP (10 microM) enhanced contractions to the activator of voltage regulated Ca2+ channels Bay K 8644. Similarly, Bay K 8644 enhanced responses to TRAP. It is concluded that the contractile response of rat aortic rings to TRAP is largely mediated by influx of extracellular Ca2+. Furthermore, the intracellular Ca2+ pool(s) activated appears to be different from the phenylephrine-sensitive pools, which cannot be depleted by TRAP.