Neurokinin A-induced guinea pig gallbladder contraction: Potential mechanism of action
Article first published online: 5 OCT 2004
Copyright © 1992 Wiley-Liss, Inc.
Drug Development Research
Volume 27, Issue 1, pages 53–60, 1992
How to Cite
Moummi, C. (1992), Neurokinin A-induced guinea pig gallbladder contraction: Potential mechanism of action. Drug Dev. Res., 27: 53–60. doi: 10.1002/ddr.430270106
- Issue published online: 6 MAR 2008
- Article first published online: 5 OCT 2004
- Manuscript Accepted: 30 APR 1992
- Manuscript Received: 20 APR 1992
- extracellular calcium;
- voltage-operated calcium channels
The present study was performed to examine the mechanism of action of neurokinin A (NKA) on guinea pig gallbaldder smooth muscle. Muscle strips were prepared and mounted in 10 mL tissue bath containing Krebs' solution under 1 g tension. NKA induced a concentration-dependent increase in gallbladder muscle tension and reached a maximal response at 1 μM. The EC50 value was approximately 30nM. Preincubation of the muscle strips with neurotoxins, tetrodotoxin (1 μM), or omega-conotoxin (0.1 μM) had no effect on the NKA contractile response. NKA-induced gallbladder contractions were insensitive to cyclooxygenase inhibitors (5 μM) piroxicam and indomethacin. In contrast, the calcium channel blockers verapamil and diltiazem (0.1–1 μM) significantly blocked the contractile response to NKA. The intracellular calcium chelator BAPTA/AM had no significant effect on NKA activity. The removal of extracellular calcium, however, completely abolished the contractile response of NKA. These data suggest that NKA has a direct contractile effect on guinea pig gallbladder smooth muscle, which is independent of prostaglandin release. The primary source of calcium involved in mediating the NKA contractile response is the extracellular pool, suggesting that NKA might act via activation of L-type voltage-operated calcium channels to mediate its action. © 1992 Wiley-Liss, Inc.