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Biomedical subjects

E Grana

Publications and source records attributed to E Grana.

At least 55 records · Page 3Linked to original sources
PubMed1984

Inhibition of norepinephrine- and 5-hydroxytryptamine-induced contraction on rat aorta by dihydroergocristine.

Norepinephrine (NE), 5-hydroxytryptamine (5-HT) and tyramine (Tyr) elicited concentration-related contractile responses on rat aorta strips. The maximum contractile responses evoked by 5-HT and NE were comparable; on the contrary the maximum response induced by Tyr was only 50% that of NE. Pretreatment with reserpine failed to modify the concentration-response curve for both Tyr and 5-HT. 5-HT concentration-response curves antagonized competitively by methysergide, 5-HT may be assumed to act directly on 5-HT receptors. The concentration-response curve for NE was shifted to the right by dihydroergocristine (DHEC) and, at least in a certain dose range, the observed agonist-antagonist interaction fulfilled the condition for competitive antagonism. With higher doses a decrease of the maximum response was obtained. DHEC antagonized 5-HT in a non competitive manner, shifting to the right and flattening the dose-response curves of this agonist. The doses needed to obtain such anti-5-HT effect are not too far from those giving alpha-adrenolytic effects.

Animals↗
PubMed1984

Direct and indirect actions of 5-hydroxytryptamine on the rat isolated vas deferens.

The contractile effect of 5-hydroxytryptamine on the rat isolated vas deferens was analyzed. In tissues from reserpine-pretreated animals 5-hydroxytryptamine (1 X 10(-6) M-3 X 10(-4) M) induced effects which were much lower than those induced in tissues from normal animals; the effects of low and medium concentrations of 5-hydroxytryptamine were antagonized by methysergide, those of medium and high concentrations were inhibited by phentolamine. In tissues from normal animals 5-hydroxytryptamine-induced contractions were compared with those induced by noradrenaline. 5-Hydroxytryptamine was less potent than noradrenaline and exhibited tachyphylaxis when the time interval between two successive exposures was too short. Phentolamine and dihydroergocristine reduced the effects of 5-hydroxytryptamine at concentrations lower than those necessary to antagonize noradrenaline-induced effects. Methysergide only reduced the effects of lower concentrations of 5-hydroxytryptamine. Cross-protection experiments showed that when noradrenaline was added before dibenamine, responses to both 5-hydroxytryptamine and noradrenaline were maintained to a very similar degree, while when 5-hydroxytryptamine was used as a protecting agent only a small degree of protection was found both towards noradrenaline and 5-hydroxytryptamine-induced effects. Cocaine potentiated the effects of low concentrations of 5-hydroxytryptamine while inhibiting those of high concentrations. The present study provides direct and indirect evidences that the contractile effect of 5-hydroxytryptamine on the rat vas deferens is prevailingly due to the release of noradrenaline; in the lower part of the concentration-response curve also direct effects are involved which are mediated by an interaction with both tryptaminergic "D" receptors and alpha 1-adrenoceptors.

Animals↗
PubMed1984

Mechanism of smooth muscle relaxation by rociverine.

Experiments were carried out in vitro on a new antispasmodic drug, 2-(diethylamino)-1-methylethyl-cis-1-hydroxy[bicyclohexyl] -2-carboxylate (rociverine), to elucidate further the mechanism of its smooth-muscle relaxation. On the furtrethonium contractions of rat jejunum rociverine exerts both a competitive antagonism, about 3000 times less than that of atropine, and a noncompetitive antagonism equal to that of papaverine. Both on rat vas deferens and on rabbit aorta rociverine at low doses slightly potentiates the response to norepinephrine (unrelated to any inhibition of uptakes), whereas at higher doses it depresses the maximum effect, 10 times more on the vas deferens than on the aorta. Against calcium in the same preparations rociverine behaves as a competitive antagonist with 10 times less potency than verapamil on the vas deferens and 300 times less on the aorta. In negative inotropic and chronotropic action on guinea-pig atria rociverine is 300 and 100 times, respectively, less potent than verapamil and in negative inotropic action on KCl-depolarized guinea-pig ventricular strips, whose contractility is restored by histamine, it is 70 times less potent than verapamil. In sum, the smooth-muscle relaxant action of rociverine depends on a modest antimuscarinic action and a direct myolytic action, the latter probably being due to an inhibitory action on the transmembrane fluxes of Ca2+. The potency ratio relative to verapamil indicates that the anti-Ca2+ action of rociverine is greater on the visceral smooth muscle than on cardiac and vascular muscle.

Animals↗
PubMed1984

QSAR in a series of muscarinic agents. Note V. New sets of rigid and flexible ligands.

A deeper insight of muscarinic receptor attachment points is obtained on studying new sets of rigid and flexible ligands. The quantitative analysis of the correspondence between biological response and structural ligand features confirms that pD2 values are strongly dependent on hydrophobic and steric parameters. Moreover, it is shown that receptor attachment points are interrelated and their simultaneous perturbations contribute to enhance the activity with comparable effectiveness.

Animals↗
PubMed1984

The 5-atom rule and the subclassification of peripheral postsynaptic muscarinic receptors.

The effects of five pairs of muscarinic compounds in homology relationship within each pair on peripheral postsynaptic muscarinic receptors of rat jejunum and guinea-pig atria and trachea were studied. The relative activities within each pair of compounds were similar for all the biological responses studied. It is reasoned that, at least in the tissues examined, the resemblance between the agonist receptors must be very close.

Acetylcholine↗
PubMed1983

A comparison of the blocking effect of alpha-adrenoceptor antagonist drugs towards directly and indirectly acting agonists on the rat vas deferens.

The antagonistic effect of dihydroergocristine and phentolamine towards the directly acting amine noradrenaline and the indirectly acting amine tyramine on the rat vas deferens was evaluated. It has been demonstrated that both alpha-adrenoceptor blocking drugs reduced the effect of the indirectly acting amine at concentrations lower than those needed to antagonize the action of noradrenaline. When concentrations of the alpha-adrenoceptor blocking drugs effective against noradrenaline were employed a qualitative difference in the antagonism towards the directly and indirectly acting amines has also been shown. It appears that in the rat vas deferens the effects induced by tyramine-released noradrenaline are more easily affected by alpha-adrenoceptor antagonist drugs than those induced by exogenously applied noradrenaline.

Adrenergic alpha-Antagonists↗
PubMed1983

Action of papaverine and verapamil on norepinephrine and calcium evoked contraction of vascular and non vascular smooth muscle.

On isolated rat vas deferens both papaverine and verapamil show a non competitive antagonism against norepinephrine and a competitive antagonism against Ca2+. Verapamil is nearly 100 times more active than papaverine. On the main pulmonary artery and on the thoracic aorta of the rabbit, verapamil shows a competitive antagonism against both norepinephrine and Ca2+ but it is more effective (almost 100 times) against Ca2+ than norepinephrine. Papaverine also shows a competitive antagonism against norepinephrine but a non competitive antagonism against Ca2+. The contrasting results obtained on rat vas deferens and rabbit vessels might be due to: 1) mechanism(s) of action of the agonist; 2) properties of the biological object as far concerns receptor activation and mechanism(s) of excitation-contraction coupling; 3) mechanism(s) of action of spasmolytic drugs. All these factors act in a cooperative way in determining the quality and the quantity of the observed responses.

Animals↗
PubMed1983

Synthesis and biological activity of heterocyclic acyl-cholines.

Five new heterocyclic acyl-cholines were synthetized through 1,3-dipolar cycloaddition and their adrenergic, cholinergic and histaminergic activity evaluated. The tested compounds did not show any significant activity; some of them, in particular the isoxazole derivative (X), shift the dose-response curve of norepinephrine to the left.

Animals↗
PubMed1983

Action of cocaine on norepinephrine- and calcium-induced contraction of vascular smooth muscle.

The action of cocaine on the norepinephrine- and calcium-induced contraction of the thoracic aorta and the main pulmonary artery of the rabbit was studied. Cocaine, depending on the employed concentrations, shows a competitive or a non-competitive antagonism against norepinephrine, while, against calcium, cocaine, at the used concentrations, shows a competitive antagonism. The results are discussed in the light of literature data obtained from different preparations of several animal species. It is clear that the actions of local anesthetics must be evaluated through a wide range of doses and by considering the properties of the biological object.

Animals↗
PubMed1982

QSAR in a series of muscarinic agents. Note IV. - New pyridine and furan derivatives.

Two new series of picolyl- and furfuryltrimethylammonium salts have been prepared and studied in order to support some hypotheses previously formulated in the study of the topology of the muscarinic receptor. The general picture of ligand interactions with receptor as seen with correlation analysis is discussed. The new quantitative structure-activity relationship is compared with those previously formulated and it is shown that biological data for new congeners are well predicted by a correlation equation published earlier.

Animals↗
PubMed1981

Actions and interactions of ergotamine and dihydroergocristine in rat aortic strips.

The stimulating actions of ergotamine and serotonin were compared with that of noradrenaline on the rat isolated aorta. The results are discussed in the light of those obtained on other vascular preparations. On ergotamine or noradrenaline contracted aortic strips the antagonist activity of dihydroergocristine in comparison with that of papaverine was studied. Both agents were able to induce dose-dependent relaxations.

Animals↗
PubMed1981

OSAR in a series of muscarinic agents. Note III--Alkyltrimethylammonium salts, ethers and esters of choline.

In the light of the experience gained studying various sets of muscarinic ligands related to a rigid model, flexible structures such as alkyltrimethylammonium salts, ethers and esters of choline have been prepared and their affinities (pD2) have been studied. The quantitative structure-activity relationships (QSAR) show that the pD2 value is strongly dependent on hydrophobic and steric parameters of the ligand substituent. Moreover, two indicator variables are considered to take ito account extra-activities connected with ligand special structural features. The overall QSAR confirm that the electrostatic attraction, the hydrophobic bonding and the polar interaction holding the ligand on the receptor are individually weak; however, these three forces collectively permit a more complete utilization of the receptor binding site.

Animals↗
PubMed1980

[Study of maximal response of the rat vas deferens. I - study of adrenergic amines with diverse mechanisms of action and the influence of cast concentration in the physiological solution].

As a preliminary to research on phenomena connected with the appearance of maximal responses in the isolated rat vas deferens greater than those obtainable with noradrenaline, the responses to noradrenaline, octopamine and thyramine under various experimental conditions are discussed. Octopamine give maximal responses which are consistently greater than those with noradrenaline but the differences are scarcely significant. Variation of the Ca2+ concentration in the physiological solution affects response to the three amines in a different way. It appears that when there is an indirect component in the mechanism of action, lack of Ca2+ has less effect on the activity of the compound.

Animals↗
PubMed1980

[Maximal response of the rat vas deferens. II. Studies on the effect of variations in external K+ and the response to noradrenaline of preparations which were depolarized and exposed to various concentrations of extracellular Ca+].

The mechanical response of the rat vas deferens observed following administration of single or cumulative doses of K+ was studied and then the influence of external Ca2+ on the K+ response was investigated. The response of the preparation to noradrenalin when the concentration of K+ and/or Ca2+ is different from the physiological one was also studied. The results indicate that the ability of K+ to increase free intracellular Ca2+ concentration is greater than that of noradrenalin; there is an increase in the maximal response to noradrenalin on increasing the external concentration of K+ and/or Ca2+.

Animals↗
PubMed1980

[Maximal response of the rat vas deferens. III. Effect of compounds with various pharmacological activities on the response to noradrenaline].

A study has been made of the action on the rat vas deferens response to noradrenalin of the following substances: cocaine, phentolamine and dihydroergocrystine; pronethalol, dichloroisopropylnoradrenalin, propranolol, N-isopropyl-p-nitrophenylethanolamine; d-chlorpheniramine; cimetidine; amitryptyline. With the exception of the beta-adrenolytic agents and cimetidine, all the compounds tested independently of their "principal" pharmacological action showed a property in common with the local anesthetics: depending on dose they were able to increase or decrease the maximal response to noradrenalin. These effects were correlated with variations in the state of stabilization of the membrane.

Animals↗