scholarly journals Proteinase-activated receptor 2 activation modulates guinea-pig mesenteric lymphatic vessel pacemaker potential and contractile activity

2004 ◽  
Vol 560 (2) ◽  
pp. 563-576 ◽  
Author(s):  
Alice K. Chan ◽  
Nathalie Vergnolle ◽  
Morley D. Hollenberg ◽  
Pierre-Yves von der Weid
2007 ◽  
Vol 292 (1) ◽  
pp. G76-G83 ◽  
Author(s):  
Muxin Wei ◽  
Kotoyo Fujiki ◽  
Eiji Ando ◽  
Sumin Zhang ◽  
Tsuyoshi Ozaki ◽  
...  

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) have opposite actions on the gallbladder; PACAP induces contraction, whereas VIP induces relaxation. Here, we have attempted to identify key residues responsible for their interactions with PACAP (PAC1) and VIP (VPAC) receptors in the guinea pig gallbladder. We synthesized PACAP-27/VIP hybrid peptides and compared their actions on isolated guinea pig gallbladder smooth muscle strips using isotonic transducers. [Ala4]- and [Val5]PACAP-27 were more potent than PACAP-27 in stimulating the gallbladder. In contrast, [Ala4, Val5]- and [Ala4, Val5, Asn9]PACAP-27 induced relaxation similarly to VIP. [Asn9]-, [Thr11]-, or [Leu13]PACAP-27 had 20–70% contractile activity of PACAP-27, whereas [Asn24,Ser25,Ile26]PACAP-27 showed no change in the activity. All VIP analogs, including [Gly4,Ile5,Ser9]VIP, induced relaxation. In the presence of a PAC1 receptor antagonist, PACAP(6–38), the contractile response to PACAP-27 was inhibited and relaxation became evident. RT-PCR analysis revealed abundant expressions of PAC1 receptor, “hop” splice variant, and VPAC1 and VPAC2 receptor mRNAs in the guinea pig gallbladder. In conclusion, PACAP-27 induces contraction of the gallbladder via PAC1/hop receptors. Gly4 and Ile5 are the key NH2-terminal residues of PACAP-27 that distinguish PAC1/hop receptors from VPAC1/VPAC2 receptors. However, both the NH2-terminal and α-helical regions of PACAP-27 are required for initiating gallbladder contraction.


1989 ◽  
Vol 67 (7) ◽  
pp. 734-739
Author(s):  
Hideharu Hayashi ◽  
Hajime Terada ◽  
Alexander Kholopov ◽  
Terence F. McDonald

The action potential configuration, developed tension, and resting tension were monitored in normoxic and hypoxic guinea pig papillary muscles superfused with solutions containing no substrate, glucose, or acetate (1–10 mM). In normoxic muscle, acetate provoked a concentration-dependent transient depression of the action potential duration and force of contraction, depression was maximal after 10–30 min, and recovery was complete after 90–120 min. In hypoxic muscle, acetate accelerated functional rundown (action potential shortening, decline of developed tension, increase in resting tension). Because rundown in hypoxic muscle was sensitive to factors affecting glycolysis (moderated by external glucose; accentuated by 2-deoxyglucose), the accentuated rundown with acetate may be accounted for by a partial block of glycolysis. However, block of glycolysis cannot explain the acetate-induced transient depression in normoxic muscle, since the depression was enhanced in normoxic muscle with 2-deoxyglucose-blocked glycolysis. We suggest that the transient depression is due to a transient depression of high energy nucleotides with consequent effects on ionic currents.Key words: acetate, action potential duration, 2-deoxyglucose, hypoxia, ATP.


1988 ◽  
Vol 66 (5) ◽  
pp. 643-647 ◽  
Author(s):  
Takeshi Katsuragi ◽  
Lulu Kuratomi ◽  
Koji Miyamoto ◽  
Tatsuo Furukawa

Interrelations between ouabain, a Na+–K+ ATPase inhibitor, and monensin, a Na+ ionophore, on noradrenaline liberation and contractile activity were evaluated in the guinea-pig vas deferens. Monensin (1 μM) per se elicited a small contraction of the tissue. However, amplitude and time to the peak of large and sustained contractions evoked by 10 μM ouabain were potentiated and markedly shortened, respectively, by monensin. Contractions elicited by ouabain with or without monensin were prevented by 3 μM phentolamine or by pretreatment with reserpine. Contractions evoked by K+-free solution were augmented by monensin. In an HPLC study, noradrenaline outflow from the vas deferens was moderately and considerably increased by monensin (10 μM) and ouabain (100 μM), respectively. The ouabain-evoked output of noradrenaline was enhanced in the presence of monensin and the time course for maximum noradrenaline release was shortened, as was the contractile activity. This enhanced outflow after ouabain plus monensin was reserpine sensitive but not tetrodotoxin sensitive. Furthermore, this noradrenaline outflow was roughly halved in Na+-deficient medium, but was unaltered in Ca2+-free medium. These findings suggest that the synergistic effect of ouabain and monensin on noradrenaline liberation from the guinea-pig vas deferens may be due to an elevation of cytoplasmic Ca2+ concentrations, presumably resulting from a stimulation of intracellular Na+–Ca2+ exchange system, but not enhanced Ca2+ entry.


1995 ◽  
Vol 114 (7) ◽  
pp. 1383-1390 ◽  
Author(s):  
Bruno Battistini ◽  
Mandy Woods ◽  
Luke J.D. O'Donnell ◽  
Timothy D. Warner ◽  
Roger Corder ◽  
...  

1990 ◽  
Vol 183 (5) ◽  
pp. 1725 ◽  
Author(s):  
E. Barocelli ◽  
M. Chiavarini ◽  
G. Morini ◽  
V. Ballabeni ◽  
A. Gentile ◽  
...  

2012 ◽  
Vol 11 (6) ◽  
pp. 51-58 ◽  
Author(s):  
I. V. Kovalyov ◽  
M. B. Baskakov ◽  
S. V. Gusakova ◽  
T. A. Vtorushina ◽  
A. S. Zheludeva ◽  
...  

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