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Antagonism by (D-Pro2, D-Trp7,9)-substance P of the cerebrovascular dilatation induced by substance P. 1982

L Edvinsson, and J McCulloch, and S Rosell, and R Uddman

The effects of (D-Pro2, D-Trp7,9)-substance P, a structural analogue of substance P, were examined in two models on cerebrovascular responses to substance P(SP) in cats; in vitro using segments of the middle cerebral artery and in situ by microapplication of the peptides close to pial arterioles. (D-Pro2, D-Trp7,9)-SP in concentrations up to 6.6 x 10(-6) M was without significant effect upon isolated middle cerebral arteries under normal conditions and in arteries contracted with prostaglandin F2 alpha. SP caused concentration-dependent relaxations of middle cerebral arteries contracted by prostaglandin F2 alpha (mean +/- SE; EC50: 2.0 +/- 1.6 x 10(-9) M). The presence of (D-Pro2, D-Trp7,9)-SP shifted the concentration-response curve of SP towards higher concentrations without significantly effecting the maximum response of the arteries to SP. A relaxation by 24.2 +/- 4.0% (n = 6) was obtained in prostaglandin F2 alpha contracted arteries by increasing the potassium concentration with 2 mM in the buffer solution. This response to potassium was unaltered in the presence of 6.6 x 10(-6)M of (D-Pro2, D-Trp7,9)-SP (25.0 +/- 7.1%, n = 5). Perivascular microapplication of SP around individual pial arterioles in situ effected dose-dependent increases in vascular calibre (mean response 14.5 +/- 2% with SP, 10(-7)M). The concomitant perivascular administration of (D-Pro2, D-Trp7,9)-SP (6.6 x 10(-6)M), which alone did not alter the arteriolar calibre, attenuated significantly the cerebrovascular response to SP (mean response 1.5 +/- 3.2%). On the basis of the agonist-antagonist relation found, these observations point to the possibility of a specific SP receptor site in cerebral arteries and arterioles.

UI MeSH Term Description Entries
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011460 Prostaglandins F (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. PGF
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002536 Cerebral Arteries The arterial blood vessels supplying the CEREBRUM. Arteries, Cerebral,Artery, Cerebral,Cerebral Artery
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
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
D001160 Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteriole
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
D014664 Vasodilation The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE. Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation

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