In vivo inhibition of tissue kallikreins by kininogen sequence analogue peptides.

Advances in Experimental Medicine and Biology
H OkunishiN Toda

Abstract

Kininogen sequence analogs containing amino acid residues around the Arg-Ser cleavage site of bovine kininogens were prepared with bulky aliphatic residues in P3 position. KKI-7 (containing a cyclohexylacetyl group) and KKI-8 (containing an adamantaneacetyl group) both inhibited human urinary kallikrein (HUK) with Ki of 4 microM. These inhibitors were 40 times more potent than the corresponding peptide containing the naturally occurring Pro at P3 and were one-seventh as susceptible to hydrolysis by HUK. Rat submaxillary kallikrein (RSK) and porcine pancreatic kallikrein (PPK) were also inhibited by these analogs. Both analogs were poor inhibitors of human plasma kallikrein, while their capacity to inhibit bovine trypsin was 1/3 and 1/17, respectively, that to inhibit HUK. In a rat blood flow study, KKI-7 infusion depressed the response to injected RSK. The response gradually returned toward normal 30 to 60 min after the infusion was terminated. Blood flow increase of dog jejunal artery in response to infused PPK was blunted by the simultaneous local infusion of Trasylol, KKI-7, or KKI-8, whereas these infusions did not alter the response to infused bradykinin. The vehicle infusion did not attenuate the response either to PPK or...Continue Reading

Citations

Jun 11, 1999·Japanese Journal of Pharmacology·A DendorferP Dominiak

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.