Related Experiment Videos
Characterization of Gaddum's substance R
G J Douglas1, K I Williams, R J Flower
1Pharmacology Group, School of Pharmacy and Pharmacology, Univesity of Bath.
British Journal of Pharmacology
|April 1, 1991
Summary
Gaddum's substance R, released from rat intestine, is an oxytocic and kininogenase enzyme. It differs from urinary kallikrein due to its susceptibility to soybean trypsin inhibitor.
Area of Science:
- Biochemistry
- Pharmacology
- Physiology
Background:
- The isolated rat intestine releases an oxytocic principle, Gaddum's substance R.
- Substance R exhibits oxytocic activity and is detectable for up to 8 hours.
Purpose of the Study:
- To characterize the biochemical properties of Gaddum's substance R.
- To differentiate substance R from known kininogenases like urinary kallikrein.
Main Methods:
- Perfusion of isolated rat intestine, biochemical assays (boiling, thioglycolate treatment), pharmacological antagonist testing (atropine, methysergide, indomethacin), guinea-pig ileum assays with kininogen, Trasylol and soybean trypsin inhibitor (SBTI) inhibition studies, and gel filtration for molecular weight determination.
Main Results:
- Substance R's oxytocic activity is heat-labile but resistant to thioglycolate and unaffected by atropine, methysergide, or indomethacin.
- Substance R and urinary kallikrein both induce contractions in guinea-pig ileum in the presence of kininogen, acting as kininogenases.
- Both activities of substance R and urinary kallikrein are inhibited by Trasylol, but only substance R's activities are selectively inhibited by SBTI.
- Gel filtration indicated a molecular weight of approximately 40 kDa for substance R.
Conclusions:
- Gaddum's substance R is a kininogenase enzyme.
- Substance R can be distinguished from plasma kallikrein by its molecular weight and from urinary kallikrein by its sensitivity to SBTI.
- The precise identity of substance R requires further investigation.