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Biomedical subjects

I Takayanagi

Publications and source records attributed to I Takayanagi.

At least 181 records · Page 10Linked to original sources
PubMed1986

Pharmacological actions of leukotrienes C4, D4 and E4 on guinea pig isolated taenia caecum as a preparation to study leukotrienes.

The contractile effects of leukotrienes (LTs) C4, D4 and E4 were studied in guinea pigs isolated taenia caecum. LTs C4, D4 and E4 contracted taenia caecum at low concentrations in a concentration-dependent manner. The response to LTs was not influenced by a gamma-glutamyl transpeptidase inhibitor (L-serine borate), aminopeptidase inhibitor (L-cysteine) or cyclooxygenase inhibitor (flurbiprofen), suggesting that LTC4 and LTD4 were not metabolized or metabolized only slightly in the guinea pig isolated taenia caecum, and that each of the LTs showed the direct contractile action. Furthermore, FPL55712 antagonized the response to LTD4 and LTC4 competitively but not that to LTE4. These results suggested that the guinea pig isolated taenia caecum is useful preparation to study the pharmacological actions of LTs.

Animals↗
PubMed1986

Some properties and mechanisms of thymol-induced release of calcium from the calcium-store in guinea-pig taenia caecum.

The properties and mechanisms of Ca release induced by thymol from the intracellular Ca-store in the guinea-pig taenia caecum were investigated and compared with those by carbachol, using an intact muscle and a microsomal fraction. In Ca, Na-free, EGTA-containing K-solution, a transient contraction was evoked by each drug, and carbachol produced the contraction following treatment with thymol; however, a reversed sequence did not. The efflux of preloaded 45Ca in the presence and absence of ATP from taenia microsomes was accelerated by increasing concentrations of Ca ions outside. The minimal concentration to stimulate 45Ca-efflux was below 0.2 microM in both cases, and the Km values for Ca ions in the presence and absence of ATP were estimated to be 0.65 microM and 2.0 microM Ca ions, respectively. Thymol, which has been reported to be one of the most potent stimulators of the Ca-induced Ca release in the sarcoplasmic reticulum of skeletal muscle, enhanced the 45Ca-efflux from the taenia microsomes in the presence of ATP dose-dependently, and its mode of action seemed bimodal. That is, at 0.5 mM, thymol lowered the concentration of Ca ions which are needed to induce stimulation of 45Ca-efflux, whereas, at 1 mM, the stimulative effect of thymol on 45Ca-efflux was to augment the maximum rate of 45Ca-efflux, independent of concentrations of Ca ions. Carbachol (1 mM) did not have an effect on 45Ca-efflux with or without 0.1 mM GTP. In conclusion, the possibility has been suggested that in the guinea-pig taenia caecum, carbachol might release stored Ca ions via unknown pathway(s), whereas thymol directly releases Ca ions in a ATP-regulated fashion. Further, carbachol would be more efficacious for releasing stored Ca ions. Notwithstanding, the Ca-stores and/or the Ca-releasing mechanisms, which are utilized by both thymol and carbachol, seemed to share a common part(s) to some degree.

Adenosine Triphosphate↗
PubMed1986

A difference in alpha-adrenoceptor mechanisms in vasa deferentia isolated from young and old rats.

A difference in alpha-adrenoceptor mechanisms in vasa deferentia isolated from 3 weeks old and 40 weeks old rats were studied by analysis of the concentration-response curve of norepinephrine and Scatchard plot of specific [3H]-prazosin binding to microsomal fractions. The efficacy of norepinephrine and capacity of the maximum binding sites of [3H]-prazosin estimated in 40 weeks old rats were larger than those in the 3 weeks old rats, while there was no difference in the affinity of norepinephrine estimated in the 3 weeks old rats and in the 40 weeks old rats. The increase of efficacy for norepinephrine in the vas deferens from the 40 weeks old rats is due to the increase in the total concentration of alpha-adrenoceptors.

Aging↗
PubMed1986

Difference in mode of action of alpha 1-adrenoceptor antagonists on some vascular smooth muscles and efficacy.

Effect of YM-12617, a selective and potent alpha 1-adrenoceptor antagonist on dose-response curves of alpha 1-adrenoceptor agonists, norepinephrine, phenylephrine and naphazoline, was tested in isolated rabbit vascular smooth muscles such as the femoral vein, portal vein and aorta. YM-12617 shifted the dose-response curves for norepinephrine and phenylephrine to the right and also declined the maximum response in the femoral vein, where norepinephrine and phenylephrine behaved as low efficacy agonists. Similar results were obtained on the curve of naphazoline in the portal vein, where the efficacy of naphazoline was low. However, the efficacies of norepinephrine, phenylephrine and naphazoline were high in the aorta. The dose-response curves for three alpha 1-agonists were shifted by YM-12617 in a parallel manner in the aorta. The curves of norepinephrine and phenylephrine were also shifted by YM-12617 in the portal vein, where the efficacies of both the alpha 1-agonists were high. The present results suggest that the mode of antagonism between the alpha 1-agonist and alpha 1-antagonist is dependent on the efficacy of the alpha 1-agonist which depends upon the receptor-density in the organ used.

Adrenergic alpha-Agonists↗
PubMed1986

A beta-adrenergic partial agonist (befunolol) discriminates two different affinity sites.

Interactions of beta-adrenergic partial agonists with the beta-adrenoceptor were studied in isolated guinea-pig taenia caecum. The competitive inhibition curve for specific binding of a high concentration (50 nM) of [3H]-befunolol by befunolol showed a biphasic shape, although the curve for specific binding of a low concentration (1 nM) was monophasic. All the competitive inhibition curves for specific binding of [3H]-befunolol (1 nM and 50 nM) by isoprenaline and propranolol showed monophasic shapes. These results suggest that befunolol may be able to discriminate two different binding sites of the beta-adrenoceptor: the high affinity site and the low affinity site.

Adrenergic beta-Agonists↗
PubMed1986

A difference in mode of antagonism between optical isomers of a potent selective alpha 1-adrenoceptor blocker (YM-12617) and norepinephrine in isolated rabbit iris dilator and aorta.

Optical isomers of YM-12617, a potent and selective alpha 1-adrenoceptor blocker, were tested on the rabbit iris dilator and aorta. The order of potency was R(-)-isomer greater than racemate greater than S(+)-isomer. The R(-)-isomer and racemate behaved as an essentially irreversible antagonist to norepinephrine in the iris dilator where the efficacy of norepinephrine was small, although the S(+)-isomer was a competitive antagonist. These drugs behaved as a competitive antagonist of norepinephrine in the aorta where the efficacy of norepinephrine was large.

Adrenergic alpha-Antagonists↗
PubMed1986

Pharmacological effects of nalorphine and nalorphine-7,8-oxide (nalorphine-epoxide): interaction of the intrinsic activity, affinity and pharmacological responses.

We examined the relationship between the pharmacological effects and the interactions of the receptors of nalorphine and its epoxide. The abilities of nalorphine-epoxide to displace [3H]-dihydromorphine (mu-site) and [3H]-ethylketocyclazocine (kappa-site) were practically equal to those of the parent compound, nalorphine, using binding assay to the rat brain membrane preparations. Furthermore, the affinities of mu- and kappa-receptors are virtually uninfluenced by epoxidation of the 7,8-double bond of nalorphine using electrically stimulated mouse and rabbit vasa deferentia. The intrinsic activity of nalorphine, however, is considerably decreased by epoxidation. Moreover, the antagonistic effect of nalorphine to the morphine-induced antinociception (via mu-receptors) was little influenced by epoxidation, but the antinociceptive effect of nalorphine using the acetic acid writhing test was considerably reduced by epoxidation. These results suggest the presence of a higher receptor capacity for the antinociception mediated through kappa-receptors and that the differences between the pharmacological responses of nalorphine and its epoxide are due to the differences of their intrinsic activities.

Analgesics↗
PubMed1985

Possible involvement of substance P immunoreactive nerves in the mediation of nicotine-induced contractile responses in isolated guinea pig bronchus.

Nicotine-induced contraction of the isolated guinea pig bronchial preparation was abolished by capsaicin and a substance P (SP) antagonist [( D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP). Nicotine increased the release of immunoreactive SP from the preparations. The nicotine-evoked release of immunoreactive SP from the bronchial preparation was reduced by hexamethonium but not by tetrodotoxin. The results indicate that the responses to nicotine of the guinea pig bronchial preparation were mediated through the release of SP-like material(s), and that the nicotine-induced response may be produced through a process independent of the sodium action potential. In conclusion, the most likely site of action of nicotine in the isolated guinea pig bronchial preparation is the nicotinic receptor of SP immunoreactive nerves.

Animals↗
PubMed1985

Some pharmacological effects of tizanidine on smooth muscle organs and alpha 2-adrenoceptor.

Microsomal and crude synaptosomal fractions were prepared from the longitudinal muscle of guinea-pig ileum. A specific binding of [3H]yohimbine (10 nM) to alpha 2-adrenoceptor in the crude synaptosomal fraction was inhibited by tizanidine and clonidine. Tizanidine is about one-third as potent as clonidine. A specific binding of [3H]QNB (0.3 nM) to muscarine receptor in the microsomal fraction was inhibited by atropine (10(-8)-10(-7) M) but not by tizanidine (up to 10(-4) M). Tizanidine inhibited spontaneous movements of guinea pig ileum and rat stomach (in situ) and intestinal transit in mice, and induced mydriasis in mice. These effects induced by tizanidine might be due to activation of alpha 2-adrenoceptor but not to atropine like action.

Animals↗
PubMed1985

A beta-adrenoceptor blocking agent, befunolol as a partial agonist in isolated organs.

A beta-adrenoceptor blocking agent, befunolol, which is clinically used in the treatment of glaucoma in Japan, was found to have intrinsic sympathomimetic activities in isolated right atria, trachea and taenia caecum of guinea pig (intrinsic activities are 0.22-0.28). The pD2-values of befunolol estimated in the isolated organs were significantly different from its pA2-values against isoprenaline. A possible explanation of our findings would to be as follows: befunolol interacts with the beta-adrenoceptor where there may be two different sites: one site for agonistic action and the other for competitive antagonistic action. Both sites are supposed to be mutually exclusive through unknown mechanisms. The intrinsic activity of befunolol may be equal to its selectivity for both the sites.

Adrenergic beta-Agonists↗
PubMed1985

Interaction of muscarinic drugs with their receptor.

Interaction of muscarinic drugs with their receptor was studied in the logitudinal muscle of guinea pig ileum. The pD2-value, the index for agonistic activity of a partial agonist was practically equal to its pA2-value, the index for competitive antagonistic activity and to its pKA-value which was a negative logarithm of a dissociation constant (KA), suggesting that the muscarinic drugs such as full and partial agonists and a competitive antagonist interacted with one binding site in the muscarinic receptor. Effects of a GTP-analogue, Gpp(NH)p (guanyl-5'-y limidodiphosphate) decreased affinities of full and partial agonists to the muscarinic receptor in a manner that was correlated with their efficacies. A relationship between the Hill's coefficients of the muscarinic drugs and their efficacies suggest that the ability to distinguish the agonist binding sites was related to their efficacy.

Animals↗
PubMed1985

Newly synthesized alpha 1-adrenoceptor blockers (SM911 and SM2470) and characterization of alpha-adrenoceptors in rat aortic strips, rat vas deferens preparations and rabbit aortic strips.

Alpha 1-adrenergic potencies of SM911 and SM2470, whose chemical structures are similar to that of prazosin, a selective alpha 1-adrenoceptor blocker, were tested in rabbit aortic strips, rat aortic strips and rat vas deferens preparations. SM2470 was as potent as prazosin in alpha 1-adrenoceptor blocking effects, though SM911 was 0.5-0.1 as potent as prazosin. The pA2-values for prazosin, SM911 and SM2470 were approximately one order of magnitude lower in rabbit aortic strips and rat vas deferens preparations than in rat aortic strips, suggesting that alpha 1-adrenoceptors in these tissues may not be identical. SM911 and SM2470 as well as prazosin did not interact with alpha 2- and beta-adrenoceptors, muscarinic and nicotinic cholinoceptors, and histamine and serotonin receptors in doses up to 10(-5) M.

Adrenergic alpha-Antagonists↗
PubMed1985

Intrinsic activity and effects of guanyl-5'-yl imidodiphosphate, Gpp(NH)p and sodium ion on the affinity of dynorphin 1-13, nalorphine and nalorphine-7,8-oxide to kappa-opioid receptor.

Nalorphine and nalorphine-7,8-oxide (nalorphine epoxide) behaved as partial agonists on the kappa-receptor in the electrically stimulated mouse vas deferens. The effects of a GTP-analogue, GppNHp and Na+ on the inhibition of [3H]ethylketocyclazocine binding by dynorphin 1-13, nalorphine, its epoxide and naloxone (antagonist) were studied with a synaptosomal fraction of guinea pig brain (except a cerebellum) and compared with the intrinsic activity of the test drugs, which was estimated in the electrically stimulated mouse vas deferens. The effects of GppNHp and Na+ on the affinity of the drugs to the kappa-receptor correlated with their intrinsic activities.

Animals↗
PubMed1985

Interactions of codeine-7,8-oxide (codeine-epoxide), as a new metabolite of codeine, with multiple opiate receptors.

Interactions of codeine-epoxide, a new metabolite of codeine, with multiple opiate receptors were studied using radioligand binding assay. The ability of codeine-epoxide to displace [3H]dihydromorphine binding was the most effective among three labeled ligands, that is, [3H]dihydromorphine, [3H]-D-Ala2-D-Leu5-enkephalin and [3H]ethylketocyclazocine, suggesting that codeine-epoxide had a selectively high affinity to mu-receptors, despite the fact the affinities of codeine-epoxide to opiate receptors were slightly less potent than its parent compound, codeine. Since "sodium ratio" and "GTP ratio" on codeine-epoxide binding lay between those of codeine and naloxone, the interaction of codeine-epoxide with opiate receptors may be slightly different from that of codeine.

Animals↗
PubMed1985

Mechanism of action of nicotine on crab-eating monkey isolated bronchial smooth muscle.

Monkey (crab-eating monkey) was used as an experimental animal in this study since the pharmacological properties of isolated monkey bronchial smooth muscle were reported to be qualitatively similar to human muscle. Nicotine (10(-5)-10(-3) M) induced a phasic contraction in the isolated monkey bronchial smooth muscle preparation. The contractile response to nicotine was abolished by hexamethonium and atropine and potentiated by physostigmine but not influenced by tetrodotoxin. These results suggest that the response to nicotine was mediated through the release of acetylcholine, and that the nicotine-induced response may be produced through a sodium action potential independent process. In addition, the mechanisms of action of nicotine on the bronchial preparation of crab-eating monkey were similar to those of nicotine on the rabbit bronchial preparation but not to those on the isolated guinea-pig bronchus.

Acetylcholine↗
PubMed1985

Some characterization of the responses to substance P and other tachykinins in rabbit iris sphincter muscle.

Contractile responses to substance P, physalaemin and eledoisin, three members of the tachykinin family, were compared and characterized in rabbit iris sphincter smooth muscle. Eledoisin and physalaemin were approximately 5 times more potent than substance P, and the maximum responses to substance P and physalaemin were about 85 percent of those to eledoisin and carbachol. The contractile responses to the three tachykinins were not affected by tetrodotoxin (3 X 10(-6) M) and atropine (10(-6) M). The contractions induced by substance P and physalaemin were well sustained even after they were thoroughly washed out, whereas the eledoisin-induced contraction was rapidly ceased by removing the agonist from the bathing medium. The sustained contraction evoked by substance P or physalaemin was strongly dependent on extracellular calcium ions. Phenoxybenzamine (2 X 10(-5) M, 10 min) selectively attenuated the response to eledoisin, but not substance P or physalaemin, and concomitant incubation with excess eledoisin (10(-7) M) significantly prevented the inhibitory effect of phenoxybenzamine. The difference between responses to eledoisin and to the other peptides, substance P and physalaemin, may suggest the existence of two different receptor subtypes for tachykinins in rabbit iris sphincter smooth muscle.

Animals↗