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

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.