PMID- 8004397
OWN - NLM
STAT- MEDLINE
DCOM- 19940719
LR  - 20190512
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 111
IP  - 2
DP  - 1994 Feb
TI  - Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and 
      myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of 
      rabbit mesenteric artery.
PG  - 525-32
AB  - 1. Small strips from third-order branches of rabbit mesenteric artery 
      (approximately 150-200 microM wide) contracted in response to noradrenaline (10 
      microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution 
      containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 
      0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a 
      single, transient contraction in artery strips, while 5-HT (10 microM) failed to 
      induce any response. 2. In strips of mesenteric artery which had been 
      permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock 
      intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and 
      D-myo-inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 
      microM) induced a transient contraction. In contrast to the non-permeabilized 
      strips, contractions to noradrenaline, caffeine and IP3 were restored by prior 
      incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to 
      noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 
      microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP 
      alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery 
      strips to IP3 significantly reduced the subsequent contractile responses to 
      caffeine. Contractile responses to caffeine and IP3 were abolished by the 
      Ca(2+)-ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced 
      concentration-dependent contraction in permeabilized artery strips. In strips 
      which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the 
      subsequent addition of 5-HT (10 microM) stimulated further contraction. The 
      protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced 
      contraction, but did not alter the contraction to Ca2+. 5. In non-permeabilized, 
      endothelium-denuded segments of rabbit mesenteric artery bathed in Ca2+-replete 
      Krebs solution, noradrenaline (10 microM) stimulated a rapid, transient 
      accumulation of IP3. 5-HT(100 microM) failed to stimulate IP3 accumulation during 
      exposure periods of up to 5 min. 5-HT (100 microM)did stimulate IP3 accumulation 
      if the external K+ concentration was raised (to around 25 mM). This concentration 
      of K+ alone did not stimulate IP3 production and the 5-HT-stimulated IP3 
      accumulation in the presence of elevated extracellular [K+] was abolished by the 
      alpha l-adrenoceptor antagonist, prazosin(O.1 microM).6. These results suggest 
      that intracellular Ca2+ release does not play an important role in 5-HT-induced 
      smooth muscle contraction in the rabbit mesenteric artery. This is despite the 
      fact that a significant intracellular Ca2+ pool is present in these cells, which 
      can be discharged by either noradrenaline or IP3.However, 5-HT did stimulate 
      smooth muscle contraction in the presence of raised intracellular 
      calcium,suggesting that a component of the contraction to 5-HT will reflect an 
      increase in myofilament Ca2+sensitivity, possibly due to the activation of 
      protein kinase C.
FAU - Seager, J M
AU  - Seager JM
AD  - Department of Physiology and Pharmacology, University of Southampton.
FAU - Murphy, T V
AU  - Murphy TV
FAU - Garland, C J
AU  - Garland CJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Bacterial Toxins)
RN  - 0 (Endotoxins)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (staphylococcal alpha-toxin)
RN  - 333DO1RDJY (Serotonin)
RN  - 3G6A5W338E (Caffeine)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - SY7Q814VUP (Calcium)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Actin Cytoskeleton/*drug effects
MH  - Animals
MH  - Bacterial Toxins/pharmacology
MH  - Caffeine/pharmacology
MH  - Calcium/metabolism/pharmacology/*physiology
MH  - Cell Membrane Permeability/drug effects
MH  - Endothelium, Vascular/physiology
MH  - Endotoxins/pharmacology
MH  - Female
MH  - Guanosine Triphosphate/pharmacology
MH  - Hemolysin Proteins/pharmacology
MH  - In Vitro Techniques
MH  - Inositol 1,4,5-Trisphosphate/biosynthesis/pharmacology/*physiology
MH  - Male
MH  - Mesenteric Arteries/drug effects/metabolism
MH  - Muscle Contraction/drug effects
MH  - Muscle, Smooth, Vascular/*drug effects/metabolism
MH  - Norepinephrine/metabolism/pharmacology
MH  - Rabbits
MH  - Serotonin/*pharmacology
PMC - PMC1909975
EDAT- 1994/02/01 00:00
MHDA- 1994/02/01 00:01
PMCR- 1995/02/01
CRDT- 1994/02/01 00:00
PHST- 1994/02/01 00:00 [pubmed]
PHST- 1994/02/01 00:01 [medline]
PHST- 1994/02/01 00:00 [entrez]
PHST- 1995/02/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1994.tb14769.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1994 Feb;111(2):525-32. doi: 10.1111/j.1476-5381.1994.tb14769.x.