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Biomedical subjects

D Regoli

Publications and source records attributed to D Regoli.

At least 361 records · Page 20Linked to original sources
PubMed1978

A new bioassay for glucagon.

1 The relaxant action of glucagon has been studied in strips of rabbit renal arteries partially contracted by a low concentration (1 ng/ml) of noradrenaline.2 The preparation was relaxed in a dose-dependent manner by concentrations of glucagon varying between 25 ng/ml and 420 ng/ml.3 The relaxant effect of glucagon (0.1 mug/ml approximately ED(60)) on this preparation was not affected by propranolol (5.0 mug/ml), cimetidine (10 mug/ml), diphenhydramine (10 mug/ml), indomethacin (5.0 mug/ml), phentolamine (1.2 mug/ml), atropine (10 mug/ml) and 8-Leu-AT(II) (1.0 mug/ml) but was slightly potentiated by Des-Arg(9) Leu-OMe(8)-Bk (25 mug/ml) and indomethacin (50 mug/ml).4 The dose-response curve to glucagon remained parallel in the presence of papaverine (2.5 mug/ml) but was shifted to the left by a factor of 2.5 to 2.8. Theophylline (250 mug/ml) also potentiated the vascular relaxation induced by glucagon.5 Insulin (10 mug/ml) did not influence the relaxant effect of glucagon.6 The removal of the N-terminal amino acid (His) of glucagon reduced by 89% the biological activity of this fragment on the vascular preparation. The removal of the C-terminal amino acids Met-27, Asn-28 and Thr-29 of glucagon resulted in a fragment which was inactive either as an agonist or as an antagonist when tested at concentrations as high as 925 ng/ml.7 It is concluded that the relaxation of partially contracted strips of rabbit renal arteries by glucagon constitutes a simple, sensitive, relatively specific and reliable bioassay which may be useful for the determination of glucagon in biological materials and for structure-activity relationship studies with this hormone.

Animals↗
PubMed1978

Rat vas deferens: a specific bioassay for endogenous opioid peptides.

The electrically-evoked contractions of the rat vas deferens were selectively inhibited by beta-endorphin, the preparation being much less sensitive to enkephalins and narcotic analgesic drugs. However, introduction of D-Ala in position 2 of [Leu]-enkephalin enhanced the activity of the opioid peptide to the order of that of beta-endorphin. It is concluded that the rat vas deferens preparation constitutes a specific bioassay for endogenous opioid peptides and related compounds.

Animals↗
PubMed1978

Synthesis of peptides by the solid-phase method. III. Bradykinin: fragments and analogs.

The natural sequence of bradykinin (BK) and 55 fragments or analogs of this peptide were perpared via the solid-phase method. The peptides were purified using ion-exchange (O-carboxymethyl(CM) and partition (Sephadex G-25) chromatography. The purity of each peptide was established by paper and thin-layer chromatography, paper electrophoresis, amino acid analysis, and biological assays. The compounds were tested in anesthetized rats (tested in vivo) and in two smooth-muscle preparations (rabbit aorta strip, cat ileum strip) in which BK produces contraction by stimulating specific receptors of different types. Some of the new peptides are interesting in that they either resist pulmonary inactivation, or are more potent than BK itself, or antagonize the myotropic effect of BK in rabbit aorta strips.

Animals↗
PubMed1978

Stimulating actions of various prostaglandins and noradrenaline in strips of rabbit renal artery.

The myotropic effects of prostaglandins E1, E2, F2alpha, A1, and noradrenaline were evaluated in spirally cut strips of rabbit renal arteries suspended in a physiological salt solution maintained at 37 degrees C. The four prostaglandins as well as noradrenaline elicited contractions of the isolated rabbit renal artery. At concentrations higher than 1.0 X 10(-7) g ml-1 the contracting effect of prostaglandin E1 diminished. The vasoconstrictor actions of prostaglandins E2 and F2alpha were potentiated by cocaine and inhibited by phentolamine. On the other hand, phentolamine did not inhibit the vasoconstrictor effect of prostaglandins E2 and F2alpha on strips of rabbit renal arteries removed from rabbits pretreated with reserpine. These results were taken as an indication that part of the contractile effects of prostaglandins E2 and F2alpha on the isolated rabbit renal artery may be due to the release of noradrenaline from adrenergic nerve terminals.

Animals↗
PubMed1978

Effects of arachidonic acid and indomethacin on the in vitro release of prostaglandins by aortic strips of spontaneously hypertensive rats.

Aortic strips removed from spontaneously hypertensive (SH) rats and preincubated with arachidonic acid (1.0 X 10(-5) g/ml) for 15 min produced two times more prostaglandin (PG) like material than aortae unexposed to the precursor of PG biosynthesis. The stimulating effect of arachidonic acid was largely inhibited by indomethacin (1.0 X 10(-5) g/ml). Also, the release of PG-like material by aortic strips derived from SH rats treated with an intravenous injection of indomethacin (10 mg/kg) was inhibited by 74% compared with the control tissues. These results raised the possibility that the in vivo conversion of arachidonic acid by large arteries of SH rats may contribute to the hypotensive effect of this PG precursor in SH rats.

Animals↗
PubMed1978

The rabbit mesenteric vein: a specific bioassay for substance P.

The anterior mesenteric vein of the rabbit responds to substance P with dose-dependent contractions and is among the vascular smooth muscles most sensitive to this peptide. In spite of its high sensitivity to numerous other agents, including angiotensin and bradykinin, the rabbit mesenteric vein can be made selective for substance P by the use of specific inhibitors that will prevent the myotropic effects of acetylcholine, catecholamines, histamine, 5-hydroxytryptamine, and of the two above-mentioned peptides, without modifying the contractions elicited by substance P. It appears that this peptide acts directly on specific receptors and not through the release of neurotransmitters. Interference by intramural prostaglandins is excluded because substance P is equally active on tissues pretreated with indomethacin or untreated. Dose-response curves obtained with substance P are close to the theoretical curves predicted by the mass action law. The rabbit mesenteric vein contains a new type of receptor for bradykinin, recently identified (REGOLI, D., MARCEAU, F., and BARABE, J. 1978. De novo formation of vascular receptors for bradykinin. Can, J. Physiol. Pharmacol. 56, in press.). The action of bradykinin on this receptor can be prevented with the use of specific and competitive inhibitors and, therefore, the mesenteric vein will distinguish between peptides of the kinins or of the substance P types.

Animals↗
PubMed1978

The effects of vasodilators in the perfused hind limbs of spontaneously hypertensive and normotensive rats.

The vascular effects of isoproterenol and nitroprusside were evaluated in the perfused hind limbs of age-matched normotensive Wistar (NW) and spontaneously hypertensive (SH) rats. The vasodilating effects of these two compounds were assessed in the presence of concentrations of noradrenaline sufficient to raise the basal perfusion pressure to 85--110 mmHg. The sensitivity of the hind limb vessels of SH rats to the vasodilating action of isoproterenol (2.4 x 10-6--1.0 x 10-4 M) was slightly greater than that of the hind limb vessels of NW rats. On the other hand, the sensitivity to the vasodilating effect of nitroprusside (1.7 x 10-7--3.3 x 10-5 M) was similar in the hind limb vessels of both groups of rats. Propranolol (7.6 x 10-6 M) inhibited to a similar extent the isoproterenol-induced dilation of NW or SH hind limb vessels, but did not modify the vasodilating effect of nitroprusside in these preparations, thus suggesting that the vasodilating action of isoproterenol was due to the stimulation of vascular beta-adrenergic receptors. These results do not support the hypothesis suggesting the existence of a deficient vascular relaxation in hypertensive rats.

Animals↗
PubMed1978

Chronotropic and inotropic effects of neurotensin on spontaneously beating auricles.

Synthetic neurotensin (NT) was shown to exert a potent positive inotropic and chronotropic action in spontaneoulsy beating guinea pig and rat auricles and to be inactive in the rabbit auricles. The positive inotropic effects of NT in guinea pig and rat auricles were detected at concentrations as low as 3.0--6.0 x 10-10 M. Maximal concentrations of NT (3.1 X 10-7 M) increased the amplitude of contractions by 135 and 55% in guinea pig and rat auricles, respectively. On the basis of ED50 values, NT was found to be 20--30 times more potent than epinephrine in increasing the force of contraction in guinea pig and rat auricles. The results suggested that the positive inotropic and chronotropic actions of NT are species dependent. The potential usefulness of NT in the treatment of experimentally induced heart failure is underlined.

Animals↗
PubMed1978

De novo formation of vascular receptors for bradykinin.

Two different types of receptors for bradykinin have been found in isolated veins of the rabbit. The first receptor is a stable component of the smooth muscle membrane and it is found in the jugular vein, while the second is generated de novo during incubation in vitro and it is present in the mesenteric vein. Actinomycin D and cycloheximide block the generation of receptors in the mesenteric vein, without exerting any action either on receptors for other agonists (e.g. substance P) in the same tissue, or on the other receptor for bradykinin in the jugular vein.

Animals↗
PubMed1978

Photoaffinity labeling of the angiotensin II receptor; pharmacology of the labeling peptides in the dark.

The biological activities of photoaffinity labeling analogs of angiotensin II (ATII) and their precursors were measured in rabbit aorta strips in the dark. Most of the analogs behave as reversible, specific agonists, one as a competitive inhibitor. The activities are discussed in line with the current view of structural requirements. The modifications consisted of substitutions on the aromatic nuclei of Tyr4 and Phe8 in [Sar1]ATII with (4'-NO2) Phe, (4'-NH2)Phe, (4'N3)Phe, (4'-N2 +)Phe, and (4'-NH2-3', 5'-I2)Phe. It is shown that the affinity of the ATII analogs modified in position 4 depends on the electronegativity and not on space-filling properties of the aromatic residue; rising electronegativity lowers the affinity, i.e. [sar1, (4'-NO2)Phe4]ATII has no more measurable activity. Substituting the aromatic side chain in position 8 of [Sar1]ATII gives well-binding analogs with intrinsic activities from 0 to 100% and activity seems to depend only on stereochemical requirements. Agonists and partial agonists bear rather small groups like -NH2, -N3, -NO2, and -N2 +. The only antagonist [Sar1, (4'-NH2-3',5'-I2)Phe8]ATII resembles the antagonist E1Sar1, Leu8]ATII in competitivity and binding.

Angiotensin II↗
PubMed1978

The effect of an acute or chronic treatment with indomethacin on the blood pressure of DOCA/salt and spontaneously hypertensive rats.

The intravenous infusion of indomethacin (5 mg/kg/min) for 10 min did not modify the systolic blood pressure of conscious, unrestrained doca/salt hypertensive, spontaneously hypertensive (SH) and normotensive Wistar (NW) rats. However, this dose of indomethacin was sufficient to prevent completely the hypotensive action of arachidonic acid in these animals. The chronic administration of indomethacin to doca/salt treated- and young SH rats was without any effect on the development of hypertension in these animals. These results suggest a limited role for endogenous PGs during the development of these two types of hypertension.

Animals↗
PubMed1978

Enhanced 5-F.U. mortality in rats eating definded formula diets.

Rats eating nutritionally adequate defined-formula diets (D.F.D) before and following lethal i.p. injection of 5-fluorouracil exhibit increased mortality and shorter survival time than rats eating conventional Purina rat chow. Neither the presence of proteins in hydrolyzed form nor the nitrogen level in the D.F.D appear to be the crucial factor of enhanced lethality. The possible mechanisms and implications of the phenomenon are discussed.

Animal Feed↗
PubMed1978

The role of diet on 5-fluorouracil toxicity.

In three experiments performed at two month intervals, rats eating a nutritionally adequate defined-formula diet (DFD) exhibit a remarkable similarity in the response to 5-FU as measured by survival time, leukopenia and weight loss. Conversely, the corresponding control groups eating the standard Purina rat food show a different degree of tolerance to 5-FU, which varies from a level similar to that of the DFD groups to twice that value. It is suggested that certain protective factors against 5-FU toxicity present in natural food are absent in formula diets produced on the basis of standard requirements for normal growth and nutrition. The present studies indicate that such protective factors are neither vegetable fibers nor arachidonic acid. The importance of food intake in experimental toxicology and clinical pharmacology is emphasized.

Animals↗
PubMed1977

Conformational features of bradykinin. A circular dichroism study of the aromatic side-chains.

The circular dichroism (CD) of the peptide hormone bradykinin and its analogues, [Phe(H4)5]-bradykinin, [Phe(H4)8]bradykinin, [Phe(H4)5,8]bradykinin, [TyrOMe5]bradykinin, [TyrOMe8]bradykinin and [TyrOMe5.8]bradykinin, is described. The comparison of the CD spectra of these analogues with each other, recorded under a variety of conditions (pH, solvent, temperature), allows the monitoring of the behaviour of the aromatic side-chains (phenylalanine, tyrosine) and an estimation of their respective spectral contributions in both spectral regions (320-250 nm, 250-190 nm) with good precision. Conformational non-equivalence of the residues Phe-5 and Phe-8 together with some overall conformational features of bradykinin are thus established.

Bradykinin↗
PubMed1977

Does indomethacin antagonize the effects of peptides and other agents on the coronary circulation of rabbit isolated hearts.

The coronary vasodilator effects of substance P, bradykinin, eledoisin, adenosine, and nitroglycerin have been tested in rabbit isolated hearts perfused with physiological medium. It has been found that substance P is the most potent vasodilator and that the peptides are 10-100 times as active as adenosine and nitroglycerin. The effect of bradykinin is reduced by 50% in the presence of indomethacin (2.8-5 X 10(-6) M) while the actions of the other vasodilator are not influenced. At such concentrations, indomethacin is inactive on its own and blocks the effects of small and intermediate doses of arachidonic acid, the prostaglandin precursor. It suggested that edogenous prostaglandins do not play any major role in mediating the coronary vasodilation produced by several peptide and nonpeptide agents, but may account for about 50% of the effect of bradykinin.

Animals↗