Discovery and characterization of an inhibitory angiotensin receptor in the guinea-pig ileum. 1994

C F Smith, and K J Taylor, and E M Whiting
ZENECA Pharmaceuticals, Cardiovascular Department, Macclesfield, Cheshire, England.

Using nitrendipine to block the smooth muscle contractile effects of angiotensin II, it has been shown that the agonist produces a dose-related inhibitory effect on the electrically stimulated, longitudinal smooth muscle, myenteric plexus preparation from the guinea-pig. In the absence of stimulation, there is no detectable direct relaxant effect of angiotensin II on the preparation, even when it is partially contracted with carbachol, leading to the conclusion that the inhibitory effects of angiotensin are mediated via prejunctional receptors on the neuron. A number of angiotensin antagonists, including DUP753, saralasin, SKB108566 and several nonpeptide antagonists synthesized at ZENECA, have been investigated vs (1) the inhibitory effects of angiotensin II and (2) the direct contractile effects produced in unstimulated tissues in the absence of nitrendipine. A correlation curve comparing the results from the two sets of experiments gave a slope of 1.05 and a correlation coefficient of 0.99, providing very strong evidence that the two receptor systems are pharmacologically identical. The antagonists were further evaluated vs angiotensin II in the rat fundic strip in order to (1) determine whether there was any species variation in the receptor systems and (2) provide an example of a smooth muscle preparation uncomplicated by indirect effects of transmitters released by angiotensin, as has been reported in the guinea-pig ileum. An excellent correlation was obtained between the Ke values in the fundus and the guinea-pig ileum, indicating no difference in receptors between species or between neurons and smooth muscle.

UI MeSH Term Description Entries
D007082 Ileum The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009197 Myenteric Plexus One of two ganglionated neural networks which together form the ENTERIC NERVOUS SYSTEM. The myenteric (Auerbach's) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. (From FASEB J 1989;3:127-38) Auerbach's Plexus,Auerbach Plexus,Auerbachs Plexus,Plexus, Auerbach's,Plexus, Myenteric
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011945 Receptors, Angiotensin Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells. Angiotensin Receptor,Angiotensin Receptors,Angiotensin II Receptor,Angiotensin III Receptor,Receptor, Angiotensin II,Receptor, Angiotensin III,Receptor, Angiotensin
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005260 Female Females

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