The bradykinin analog RMP-7 increases intracellular free calcium levels in rat brain microvascular endothelial cells. 1994

S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
Alkermes, Inc., Cambridge, Massachusetts.

The vasoactive peptide bradykinin is believed to cause increased vascular permeability by the activation of B2 receptors on the vascular endothelium. A bradykinin analog, H-Arg-Pro-Hyp-Gly-Thi-Ser-Pro-4-Me-Tyr(psi CH2NH)-Arg-OH (RMP-7), was designed and it was proposed that it might increase cerebrovascular permeability by activating B2 receptors on brain microvasculature. In this report, the effects of RMP-7 and related peptides on bradykinin receptor-induced calcium signaling were examined in rat brain microvascular endothelial (RBME) cultures. RBME cells are responsive to bradykinin and exhibit specific [3H]-bradykinin binding, with Scatchard analysis indicating a major class of sites with a Kd of 3.9 +/- 1.4 nM and a minor class of higher affinity sites (Kd approximately 33 pM). RMP-7 displaces a significant component of specific [3H]-bradykinin binding from RBME cells; RMP-10, and RMP-7 diastereomer with a D-amino acid substitution in the number 9 position, does not. [3H]-bradykinin binding to RBME cells is not displaced by desArg9-bradykinin, which indicates that neither class of sites is a B1 bradykinin receptor. RMP-7 induces an increase in intracellular free calcium levels in RBME cells. The time course, magnitude and concentration dependence of RMP-7-induced calcium signaling is similar to that induced by bradykinin in RBME and other endothelial cells. Compared with RMP-7, RMP-10 is at least 1000 times less potent. However, the level of contamination by RMP-7 in the RMP-12 preparation accounts for its activity, an indication that both the RMP-10 and RMP-12 diastereomers are essentially inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008833 Microcirculation The circulation of the BLOOD through the MICROVASCULAR NETWORK. Microvascular Blood Flow,Microvascular Circulation,Blood Flow, Microvascular,Circulation, Microvascular,Flow, Microvascular Blood,Microvascular Blood Flows,Microvascular Circulations
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010539 Permeability Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions. Permeabilities
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D001920 Bradykinin A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg,Bradykinin Acetate, (9-D-Arg)-Isomer,Bradykinin Diacetate,Bradykinin Hydrochloride,Bradykinin Triacetate,Bradykinin, (1-D-Arg)-Isomer,Bradykinin, (2-D-Pro)-Isomer,Bradykinin, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (2-D-Pro-7-D-Pro)-Isomer,Bradykinin, (3-D-Pro)-Isomer,Bradykinin, (3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (5-D-Phe)-Isomer,Bradykinin, (5-D-Phe-8-D-Phe)-Isomer,Bradykinin, (6-D-Ser)-Isomer,Bradykinin, (7-D-Pro)-Isomer,Bradykinin, (8-D-Phe)-Isomer,Bradykinin, (9-D-Arg)-Isomer,Arg Pro Pro Gly Phe Ser Pro Phe Arg
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein

Related Publications

S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
September 1999, Pharmaceutical research,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
May 1998, Journal of neuro-oncology,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
February 1995, Pharmaceutical research,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
January 2003, British journal of pharmacology,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
October 1997, The American journal of physiology,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
October 1988, Pflugers Archiv : European journal of physiology,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
June 1999, Journal of neurochemistry,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
November 1994, Journal of neurosurgery,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
October 1999, Neuro-oncology,
S R Doctrow, and S M Abelleira, and L A Curry, and R Heller-Harrison, and J W Kozarich, and B Malfroy, and L A McCarroll, and K G Morgan, and A R Morrow, and G F Musso
May 2014, Journal of neuroscience research,
Copied contents to your clipboard!