Abstract
Substance P (SP) is a neurotransmitter peptide that is widely distributed in the body. Since SP has been demonstra in the gallbladder (GB) and bile ducts of dogs, it may have a role in biliary motility. The objective of this study was to examine the effect of SP on the GB and sphincter of Oddi (SOD) of dogs in vitro, to evaluate the structure-activity relationship of SP, and to compare the contractile effect of SP with that of cholecystokinin octapeptide (CCK-8) and acetylcholine (Ach). Isolated longitudinal strips of GB and SOD from dogs were suspended in oxygenated Krebs buffer and the isometric tension responses to various doses of CCK-8, Ach, SP, and SP homologs [SP-free acid (SPFA), Octa-SP (O-SP), physalaemin (PHY)] were measured. We found that all the SP homologs, other than SPFA, stimulated GB and SOD contractions in vitro in a dose-dependent manner. The potency of SP and its homologs on GB and SOD was SP ≥PHY > O-SP; SPFA was without effect. CCK-8 was significantly more effective than SP on GB contraction, but unlike SP, CCK had no effect on SOD. The maximum contraction achieved by Ach was 1.3 (SOD) to 2.3 (GB) times greater than that achieved by SP, but the ED50of SP was approximately 100- to 200-fold lower than that of Ach. The contractile effect of SP was partially blocked by 10-5M atropine. We suggest from the above results that contractile effects of SP on the dog GB and SOD are probably mediated through binding to specific SP receptors that require the C-terminal amino group and the C-terminal penta-peptide sequence in order to be most effective.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 812-817 |
| Number of pages | 6 |
| Journal | Digestive Diseases and Sciences |
| Volume | 34 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1989 |
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Keywords
- acetylcholine
- cholecystokinin
- gallbladder
- motility
- sphincter of Oddi
- substance P
ASJC Scopus subject areas
- Gastroenterology
Cite this
Contractile response of canine gallbladder and sphincter of Oddi to substance P and related peptides in vitro. / Guo, Yan Shi; Singh, Pomila; Gomez, Guillermo; Rajaraman, Srinivasan; Thompson, James C.
In: Digestive Diseases and Sciences, Vol. 34, No. 6, 06.1989, p. 812-817.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Contractile response of canine gallbladder and sphincter of Oddi to substance P and related peptides in vitro
AU - Guo, Yan Shi
AU - Singh, Pomila
AU - Gomez, Guillermo
AU - Rajaraman, Srinivasan
AU - Thompson, James C.
PY - 1989/6
Y1 - 1989/6
N2 - Substance P (SP) is a neurotransmitter peptide that is widely distributed in the body. Since SP has been demonstra in the gallbladder (GB) and bile ducts of dogs, it may have a role in biliary motility. The objective of this study was to examine the effect of SP on the GB and sphincter of Oddi (SOD) of dogs in vitro, to evaluate the structure-activity relationship of SP, and to compare the contractile effect of SP with that of cholecystokinin octapeptide (CCK-8) and acetylcholine (Ach). Isolated longitudinal strips of GB and SOD from dogs were suspended in oxygenated Krebs buffer and the isometric tension responses to various doses of CCK-8, Ach, SP, and SP homologs [SP-free acid (SPFA), Octa-SP (O-SP), physalaemin (PHY)] were measured. We found that all the SP homologs, other than SPFA, stimulated GB and SOD contractions in vitro in a dose-dependent manner. The potency of SP and its homologs on GB and SOD was SP ≥PHY > O-SP; SPFA was without effect. CCK-8 was significantly more effective than SP on GB contraction, but unlike SP, CCK had no effect on SOD. The maximum contraction achieved by Ach was 1.3 (SOD) to 2.3 (GB) times greater than that achieved by SP, but the ED50of SP was approximately 100- to 200-fold lower than that of Ach. The contractile effect of SP was partially blocked by 10-5M atropine. We suggest from the above results that contractile effects of SP on the dog GB and SOD are probably mediated through binding to specific SP receptors that require the C-terminal amino group and the C-terminal penta-peptide sequence in order to be most effective.
AB - Substance P (SP) is a neurotransmitter peptide that is widely distributed in the body. Since SP has been demonstra in the gallbladder (GB) and bile ducts of dogs, it may have a role in biliary motility. The objective of this study was to examine the effect of SP on the GB and sphincter of Oddi (SOD) of dogs in vitro, to evaluate the structure-activity relationship of SP, and to compare the contractile effect of SP with that of cholecystokinin octapeptide (CCK-8) and acetylcholine (Ach). Isolated longitudinal strips of GB and SOD from dogs were suspended in oxygenated Krebs buffer and the isometric tension responses to various doses of CCK-8, Ach, SP, and SP homologs [SP-free acid (SPFA), Octa-SP (O-SP), physalaemin (PHY)] were measured. We found that all the SP homologs, other than SPFA, stimulated GB and SOD contractions in vitro in a dose-dependent manner. The potency of SP and its homologs on GB and SOD was SP ≥PHY > O-SP; SPFA was without effect. CCK-8 was significantly more effective than SP on GB contraction, but unlike SP, CCK had no effect on SOD. The maximum contraction achieved by Ach was 1.3 (SOD) to 2.3 (GB) times greater than that achieved by SP, but the ED50of SP was approximately 100- to 200-fold lower than that of Ach. The contractile effect of SP was partially blocked by 10-5M atropine. We suggest from the above results that contractile effects of SP on the dog GB and SOD are probably mediated through binding to specific SP receptors that require the C-terminal amino group and the C-terminal penta-peptide sequence in order to be most effective.
KW - acetylcholine
KW - cholecystokinin
KW - gallbladder
KW - motility
KW - sphincter of Oddi
KW - substance P
UR - http://www.scopus.com/inward/record.url?scp=0024364066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024364066&partnerID=8YFLogxK
U2 - 10.1007/BF01540263
DO - 10.1007/BF01540263
M3 - Article
C2 - 2470556
AN - SCOPUS:0024364066
VL - 34
SP - 812
EP - 817
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
SN - 0163-2116
IS - 6
ER -