PMID- 7792139 OWN - NLM STAT- MEDLINE DCOM- 19950727 LR - 20191210 IS - 0031-6768 (Print) IS - 0031-6768 (Linking) VI - 429 IP - 5 DP - 1995 Mar TI - Control of pulmonary vascular smooth muscle tone by sarcoplasmic reticulum Ca2+ pump blockers: thapsigargin and cyclopiazonic acid. PG - 617-24 AB - The effect of thapsigargin (TG) and cyclopiazonic acid (CPA) on the mechanical activity of the rat pulmonary artery were investigated. In chemically (beta-escin)-skinned arterial strips, application of TG (0.1-1 microM) or CPA (0.5-10 microM) prior and throughout the loading procedure of the internal Ca2+ stores (0.3 microM free Ca2+ ions for 8-10 min) concentration dependently inhibited the subsequent contractile response induced by noradrenaline (NA, 10 microM) or caffeine (25 mM). In intact strips repeatedly incubated in a Ca(2+)-containing solution (2.5 mM for 10 min), followed by incubation in a Ca(2+)-free solution 12 min before NA-stimulation, TG and CPA not only inhibited the NA-induced contraction but also increased the tension which appeared during the exposure time to Ca2+. The two phenomena developed with similar time courses. The increase in tension during the readmission of Ca2+ ions was not antagonized by verapamil (10 microM) or nifedipine (1 microM) but was blocked by La3+ (50 microM) and Co2+ (1 mM) ions. The amplitude of the verapamil-insensitive TG (or CPA)-induced contraction was dependent on the external [Ca2+] [0.1-10 mM, concentration for half maximal effect (EC50) = 0.85 mM], not modified by the reduction of the external [Na+] (from 130 to 10 mM) and decreased by depolarization of the strip using K(+)-rich (30-120 mM) solutions. Under the latter condition, 38 +/- 9 and 83 +/- 4% reduction (n = 5) was observed in the presence of 60 and 120 mM K+ respectively.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Gonzalez De La Fuente, P AU - Gonzalez De La Fuente P AD - Laboratoire de Physiologie, Universite de Bordeaux 2, France. FAU - Savineau, J P AU - Savineau JP FAU - Marthan, R AU - Marthan R LA - eng PT - Journal Article PL - Germany TA - Pflugers Arch JT - Pflugers Archiv : European journal of physiology JID - 0154720 RN - 0 (Indoles) RN - 0 (Terpenes) RN - 3G6A5W338E (Caffeine) RN - 67526-95-8 (Thapsigargin) RN - 6805-41-0 (Escin) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) RN - X4W3ENH1CV (Norepinephrine) RN - X9TLY4580Z (cyclopiazonic acid) RN - YZS2RPE8LE (Strontium) SB - IM MH - Animals MH - Caffeine/pharmacology MH - Calcium/metabolism MH - Calcium-Transporting ATPases/*antagonists & inhibitors MH - Escin/pharmacology MH - In Vitro Techniques MH - Indoles/*pharmacology MH - Male MH - Muscle Contraction/drug effects MH - Muscle Tonus/*drug effects MH - Muscle, Smooth, Vascular/*drug effects/metabolism MH - Norepinephrine/pharmacology MH - Protein-Tyrosine Kinases/antagonists & inhibitors MH - Pulmonary Artery/cytology/drug effects MH - Pulmonary Circulation/*drug effects MH - Rats MH - Rats, Wistar MH - Sarcoplasmic Reticulum/drug effects/*metabolism MH - Strontium/pharmacology MH - Terpenes/*pharmacology MH - Thapsigargin EDAT- 1995/03/01 00:00 MHDA- 1995/03/01 00:01 CRDT- 1995/03/01 00:00 PHST- 1995/03/01 00:00 [pubmed] PHST- 1995/03/01 00:01 [medline] PHST- 1995/03/01 00:00 [entrez] AID - 10.1007/BF00373982 [doi] PST - ppublish SO - Pflugers Arch. 1995 Mar;429(5):617-24. doi: 10.1007/BF00373982.