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.
Antonaccio
M J
MJ
Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Normandin
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D018179:Receptors, Thrombin / Q000187:drug effects*
D010446:Peptide Fragments; D011942:Receptors, Adrenergic, alpha; D018179:Receptors, Thrombin; C072032:thrombin receptor peptide (42-55); D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine