The competitive antagonistic effect of compounds from Mandevilla velutina on kinin-induced contractions of rat uterus and guinea-pig ileum in vitro. 1988

J B Calixto, and M G Pizzolatti, and R A Yunes
Department of Pharmacology CCB, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.

1. Pure non-peptide compounds obtained in crystal form from the crude extract of the plant Mandevilla velutina (Apocynaceae) were analysed for their antagonistic effects on rat uterine and guinea-pig smooth muscle contractions induced by bradykinin (Bk), lisyl-bradykinin (L-Bk), acetylcholine (ACh), oxytocin and histamine, in vitro. 2. Pre-incubation of rat uterine muscle with compounds MV 8608, MV 8609, MV 8610, MV 8611 and MV 8612 (5 to 40 micrograms ml-1) caused parallel and concentration-dependent rightward displacements of the Bk concentration-response curves (1 to 1000 nM). Schild plots of these data were linear (correlation close to 1) and yielded nominal pA2 values (g ml-1) of 5.7, 5.6, 5.4, 5.7 and 5.3, respectively. Compounds MV 8608, MV 8611 and MV 8612 (5 to 20 micrograms ml-1) also caused concentration-dependent and parallel displacements to the right of the concentration-response curve to L-Bk (1 to 10,000 nM). The Schild plots were linear and furnished nominal pA2 values (g ml-1) of 5.4, 5.8 and 5.1, respectively. With the exception of the antagonist effect of compound MV 8606 against Bk-induced contraction, all compounds behaved as simple competitive kinin antagonists since the calculated slopes were not different from unity. 3. In the guinea-pig ileum, both MV 8608 and MV 8612 (5 to 20 micrograms ml-1), produced concentration-dependent rightward displacements of the concentration-response curve to Bk (0.1 to 1000 nM) when the experiments were performed in the presence but not in the absence of atropine (2.5 microM). However, in contrast to the result obtained in the rat uterus, compound MV 8608 also caused a significant reduction of the maximal response to Bk. The Schild plot for compound MV 8612 was linear (correlation close to unity) and furnished a nominal pA2 value (g ml-1) of 5.3 and a slope not different from unity. 4. In rat uterine muscle, compounds MV 8608 and MV 8612 at concentrations producing marked rightward displacements of the kinin concentration-response curves (10 and 20 micrograms ml-1), did not influence the uterine contractile response to oxytocin or ACh, indicating some selectivity towards kinin receptors. Similarly, compound MV 8612 (10 and 20 ygml 1) did not interfere with the sensitivities or the maximal responses to ACh and histamine in the guinea-pig ileum, whereas compound MV 8608 (10 and 20ug ml-1) caused a slight reduction of ACh- and histamine-induced maximal contractions, allied to decrease of the sensitivity to histamine at concentrations of 20pgml-1 or more. 5. These results extend our previous data, indicating the existence of several non-peptide compounds in the crude extract of Mandevilla velutina that act as simple, competitive, selective and reversible kinin receptor antagonists in the rat isolated uterus and guinea-pig ileum 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.
D007705 Kinins A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588) Kinin
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
D010121 Oxytocin A nonapeptide hormone released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). It differs from VASOPRESSIN by two amino acids at residues 3 and 8. Oxytocin acts on SMOOTH MUSCLE CELLS, such as causing UTERINE CONTRACTIONS and MILK EJECTION. Ocytocin,Pitocin,Syntocinon
D010946 Plants, Medicinal Plants whose roots, leaves, seeds, bark, or other constituent parts possess therapeutic, tonic, purgative, curative or other pharmacologic attributes, when administered to man or animals. Herbs, Medicinal,Medicinal Herbs,Healing Plants,Medicinal Plants,Pharmaceutical Plants,Healing Plant,Herb, Medicinal,Medicinal Herb,Medicinal Plant,Pharmaceutical Plant,Plant, Healing,Plant, Medicinal,Plant, Pharmaceutical,Plants, Healing,Plants, Pharmaceutical
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
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
D005260 Female Females

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