Biomaterial Database

Effects of the tachykinin NK1 receptor antagonist, RP 67580, on central cardiovascular and behavioural effects of substance P, neurokinin A and neurokinin B. 1995

J Culman, and B Wiegand, and H Spitznagel, and S Klee, and T Unger

German Institute for High Blood Pressure Research, University of Kiel.

1. We have investigated the effects of the non-peptide NK1 tachykinin receptor antagonist, RP 67580, and its inactive enantiomer, RP 68651, on the cardiovascular and behavioural responses to substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) injected intracerebroventricularly (i.c.v.) in conscious rats. 2. The SP and NKA (25 pmol)-induced increases in blood pressure (BP) and heart rate (HR) were of the same magnitude. The cardiovascular responses to both peptides were associated with excessive grooming behaviour and wet dog shakes (WDS). Relative to SP, NKA was weaker in inducing hindquarter grooming (HG), but more effective in eliciting WDS. The cardiovascular response to NKB (50 pmol) comprised an increase in BP and HR, while the behavioural response was weak. 3. RP 67580 (100 pmol), injected 10 or 30 min prior to SP, effectively inhibited the cardiovascular and behavioural responses to the peptide whereas lower doses were ineffective. Pretreatment with 500 pmol of RP 67580, 10 or 30 min prior to SP, reduced the BP response. Of the behavioural manifestations, only face washing was attenuated when the antagonist was injected 10 min before SP. At 2500 pmol, the antagonist exaggerated the BP response to the peptide without affecting the behavioural response. RP 68651 (100 or 2500 pmol) did not modify the central responses to SP. 4. Neither RP 67580 nor RP 68651 (100 pmol), affected the cardiovascular and behavioural responses to NKA or NKB. 5. Our results indicate that RP 67580 is a selective and high affinity antagonist at central NK1 tachykinin receptors in the rat.

UI	MeSH Term	Description	Entries
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007276	Injections, Intraventricular	Injections into the cerebral ventricles.	Intraventricular Injections,Injection, Intraventricular,Intraventricular Injection
D008297	Male		Males
D002319	Cardiovascular System	The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.	Circulatory System,Cardiovascular Systems,Circulatory Systems
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001522	Behavior, Animal	The observable response an animal makes to any situation.	Autotomy Animal,Animal Behavior,Animal Behaviors
D013373	Substance P	An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.	Euler-Gaddum Substance P,Hypothalamic Substance P,SP(1-11),Euler Gaddum Substance P,Substance P, Euler-Gaddum,Substance P, Hypothalamic
D015287	Neurokinin B	A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ A with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the URINARY BLADDER and UTERUS.	Neuromedin K,Neurokinin beta
D015288	Neurokinin A	A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ B with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the BRONCHI.	Substance K,Neurokinin alpha,Neuromedin L
D015320	Tachykinins	A family of biologically active peptides sharing a common conserved C-terminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors.	Tachykinin