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Biomedical subjects

I Takayanagi

Publications and source records attributed to I Takayanagi.

At least 163 records · Page 9Linked to original sources
PubMed1987

Interactions of some partial agonists with high and low affinity binding sites in beta-adrenoceptors.

Interactions of derivatives of befunolol (BFE-37, BFE-55, and BFE-61), carteolol, and pindolol with beta-adrenoceptors were tested in guinea pig isolated taenia caecum. All the drugs used acted as partial agonists on the beta-adrenoceptors when compared with isoprenaline, a full agonist. The pA2 values of BFE-61, carteolol, and pindolol were significantly larger than their pD2 values, while there was no significant difference between the pA2 and pD2 values for BFE-37 and BFE-55. The specific binding of [3H]befunolol to microsomal fractions from the guinea pig taenia caecum distinguished two binding sites, high affinity and low affinity sites. Both sites are considered to be bound by 50 nM of [3H]befunolol. Specific 3H binding was displaced by BFE-61, carteolol, and pindolol in a biphasic manner but in a monophasic manner by BFE-37 and BFE-55. Furthermore, [3H]befunolol binding was only partially displaced by BFE-55 but completely displaced by the other drugs used. These results, together with our previous findings, suggest that BFE-61, carteolol, and pindolol discriminate between the two affinity binding sites in the beta-adrenoceptors, which are not discriminated between by BFE-37, and further that BFE-55 may bind with only the high affinity site.

Adrenergic beta-Agonists↗
PubMed1987

Noncholinergic contractile response to nicotine in the guinea pig isolated tracheal smooth muscle.

The existence of substance P immunoreactive nerves in the trachea of guinea pig is known. In this study, capsaicin induced a long-lasting and marked contraction in the guinea pig trachea and nicotine-induced contraction was partially reduced in the capsaicin-treated muscle. Furthermore, the contractile response to nicotine (10(-5) M) in the presence of atropine (10(-7) M) was abolished by a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7,9 Leu11]substance P (10(-5) M). These findings suggest that noncholinergic contractile response to nicotine may be due to the release of material(s) resembling substance P in the isolated tracheal smooth muscle preparation of guinea pig.

Acetylcholine↗
PubMed1987

A derivative of befunolol, BFE-55, interacts with only the high affinity sites in beta-adrenoceptors.

The effect of BFE-55, a derivative of befunolol (a beta-adrenergic partial agonist) on specific [3H]befunolol binding to a microsomal fraction from the guinea pig taenia caecum was tested. A Scatchard plot of specific [3H]befunolol binding in the absence of BFE-55 was concave, suggesting an existence of high and low affinity sites in beta-adrenoceptors. In contrast, the Scatchard plot of data in the presence of BFE-55 (3 X 10(-7) M) was straight. In the presence of BFE-55, the high affinity sites disappeared and the low affinity site was unaffected. In the absence and presence of BFE-55 there was no difference between the pKD values or Bmax values at the low affinity site. These findings indicate that BFE-55 interacts with only the high affinity sites in beta-adrenoceptors.

Animals↗
PubMed1987

Characteristics of beta-adrenoceptors in tracheal smooth muscle of guinea pig sensitized by egg albumin.

The effect of pretreatment with egg albumin was examined on the beta-adrenoceptors in guinea pig isolated trachea. Befunolol and carteolol acted as partial agonists and their pA2 values were significantly larger than their corresponding pD2 values in tracheae from both untreated guinea pigs and those treated with egg albumin, suggesting that the beta-adrenoceptors contain two different affinity sites. The Scatchard plot of specific [3H]befunolol binding showed two affinity sites of the receptor (high and low affinity sites) in tracheae from both untreated animals and those treated with egg albumin. The pKD values of befunolol for both low and high affinity sites were in agreement with their respective pD2 and pA2 values. The intrinsic activities of befunolol and carteolol and the pD2 values of the test drugs were decreased by the treatment with egg albumin. The treatment with egg albumin also decreased the total amount of the two affinity sites of the receptor without any change in affinity. The present results support the partial blockade of beta-adrenoceptors in asthma proposed by Szentivanyi.

Adrenergic beta-Antagonists↗
PubMed1987

A difference in pharmacological properties of histamine receptors in rabbit aorta and basilar artery.

An interaction of Ca entry blockers, D600 and diltiazem, with histamine receptors was tested in rabbit aorta and basilar artery. D600 caused a parallel rightward shift of the concentration response curve for histamine. The slope values from Schild plot analysis in aorta were not different from unity. Dibenamine pretreatment caused reduction of maximum response to histamine in aorta. Such reduction was diminished markedly by the presence of D600 or chlorpheniramine in aorta but not in basilar artery. However, diltiazem did not influence the concentration response curve for histamine. These findings suggest that pharmacological property of histamine receptors in rabbit aorta is distinct from that in basilar artery. Furthermore diltiazem seems not to interact with histamine receptors in both vascular tissues.

Animals↗
PubMed1987

Interactions of befunolol, a beta-adrenergic partial agonist, and its derivatives with high and low affinity sites in beta-adrenoceptors.

Modes of action of befunolol and its derivatives were tested in guinea pig isolated taenia caecum. The pA2-values of BFE-60 (befunolol), -61 and -69 against isoprenaline, which measures interactions with the high affinity sites on beta-adrenoceptors, were significantly larger than their pD2-values, which were equal to their pA2-values against carteolol. Carteolol is a beta-adrenergic partial agonist with higher intrinsic activity, to which the response results from interaction with low affinity sites. These results suggest that BFE-60, -61 and -69 discriminate the high and low affinity sites on beta-adrenoceptors. The pA2-values of BFE-37, -41, -47 and -72 against isoprenaline were, however, equal to their pD2-values and pA2-values against carteolol. These drugs seem to have little or no ability to discriminate between the high and low affinity sites. BFE-55 antagonized isoprenaline but not carteolol suggesting that BFE-55 interacted with only the high affinity sites.

Adrenergic beta-Agonists↗
PubMed1987

Receptor interactions of a series of imidazolines: comparison of the alpha 2-adrenoceptors between the rabbit vas deferens and guinea pig ileum.

A series of imidazolines and norepinephrine were used to characterize and differentiate the presynaptic alpha 2-adrenoceptors in the rabbit vas deferens and the guinea pig ileal longitudinal muscle using pharmacological procedures. Based on pEC50-values (the negative log of the 50% effective concentration) for each imidazoline, a rank order of potency of p-aminoclonidine greater than oxymetazoline greater than or equal to clonidine greater than naphazoline greater than phentolamine was obtained in the rabbit vas deferens and an order of p-aminoclonidine greater than clonidine greater than naphazoline greater than oxymetazoline was obtained in the guinea pig ileum. In the rabbit vas deferens, phentolamine, which is generally considered to be a competitive alpha 1- and alpha 2-adrenoceptor antagonist, acted as a full alpha 2-adrenoceptor agonist. The dissociation constants of oxymetazoline and yohimbine were significantly lower in the rabbit vas deferens than in the guinea pig ileum. These results suggest that the presynaptic alpha 2- adrenoceptors in these tissues are different. Furthermore, the pKB-value of yohimbine against norepinephrine was significantly one log unit lower than those obtained using a series of imidazolines. Data from our studies add to increasing evidence of the existence of high and low affinity binding sites on the alpha 2-adrenoceptors in the rabbit vas deferens.

Animals↗
PubMed1987

Radioligand binding studies of postsynaptic alpha 1-adrenoceptors in the rabbit iris dilators.

Interactions of several alpha 1-adrenoceptor agonists and antagonists were studied in rabbit iris dilator smooth muscles and aortic strips using radioligand binding techniques. The specific binding of [3H]-prazosin to the membrane preparations of both tissues is of high affinity, saturable with a single binding site, has characteristics expected of alpha 1-adrenoceptors. pKi-Values of prazosin and yohimbine and the pKD-value of [3H]-prazosin in the rabbit dilators, however, were significantly lower than those in the aortic strips, while pKi-values of phentolamine, clonidine and norepinephrine in the dilators were nearly equal to those in the aortic strips. Although the efficacy of norepinephrine in the dilators was significantly less than that in the aortic strips, the maximum binding sites for [3H]-prazosin to the membrane preparations from the rabbit dilators were more numerous than those from the aortic strips. Therefore, it is likely that the intrinsic efficacy of norepinephrine in the dilators is less than that in the aortic strips. These results suggest that alpha 1-adrenoceptors in the rabbit dilator smooth muscle and the aortic strips may not be identical and that both selective and nonselective drugs, which act on these receptor sites, may exist.

Animals↗
PubMed1987

A regional difference in alpha 1-adrenoceptor mechanism in canine veins.

The pD2-values for noradrenaline obtained from the veins of the body wall were quite different from those embryogenetically related to the digestive tract. Therefore, the difference in the post-junctional alpha 1-adrenoceptor mechanism was studied in venous smooth muscle preparations from the canine. The helical and longitudinal strips of the lateral saphenous, femoral and portal veins, and the inferior vena cava were prepared and set in an organ bath apparatus. The longitudinal strips of the lateral saphenous and femoral veins, and inferior vena cava did not or little respond to noradrenaline. The pD2-values for noradrenaline differed considerably among the veins, while the pA2-values for prazosin against noradrenaline were identical in all veins used. Negative log of dissociation constants, pKA-values, for noradrenaline obtained by the partial irreversible blockade of alpha 1-adrenoceptors with phenoxybenzamine were very similar in all the veins. Efficacies which were calculated by the same method differed considerably among the veins. The dissociation constants, KD-value and the maximum binding sites, Bmax-values for [3H]-prazosin were also estimated by Scatchard analysis of the specific binding of [3H]-prazosin to the microsomal fractions from veins. The KD-values for [3H]-prazosin were also identical. However, Bmax-values varied considerably among the veins. The Bmax-values are proportional to the 50% effective concentrations, whose negative logs were the pD2-values, and to the efficacies. The present results suggest that the regional difference in the pD2-values for noradrenaline in the canine veins is not due to the affinities to the alpha 1-adrenoceptors but to the receptor densities.

Animals↗
PubMed1986

Comparison of the muscarinic cholinoceptors in the rabbit ciliary body and the guinea-pig ileum.

Interactions of several muscarinic drugs with their receptors were studied in the ciliary body smooth muscle of rabbits and the ileal longitudinal muscle of guinea-pigs, using pharmacological and biochemical procedures. The dissociation constants of carbachol, pilocarpine, atropine and pirenzepine estimated by these procedures indicate no heterogeneity of muscarinic receptors in either tissue; thus both are probably of the M2 type. However, the density of the receptors in the ciliary body is lower than in the ileum. Pilocarpine, with lower intrinsic efficacy, demonstrated a pronounced organ selectivity when compared to carbachol as it was a potent full agonist in the ileum and a competitive antagonist in the ciliary body. These results suggest the importance of both receptor density and threshold as determinants of agonist potency.

Animals↗
PubMed1986

Characterization of postsynaptic alpha 1-adrenoceptors in the rabbit iris dilator smooth muscle.

Interactions of several alpha-adrenoceptor agonists and antagonists with their receptors were studied in rabbit and guinea pig iris dilator smooth muscle and rabbit aortic strips using pharmacological procedures. In rabbit iris dilators and aortic strips, noradrenaline acted as a full agonist, while oxymetazoline, clonidine and tizanidine acted as partial agonists. The dissociation constants of full and partial agonists in the dilators, calculated after irreversible blockade of a proportion of the active receptors with phenoxybenzamine, were similar to those in the aortic strips. Furthermore, the relative intrinsic efficacies of partial agonists were practically equal in the two tissues, suggesting that these drugs act on the same alpha-adrenoceptors. Since the alpha 2-agonists clonidine and tizanidine had low affinity in the rabbit dilators, the alpha-adrenoceptors in this tissue appear to be of alpha 1-type. These results were further supported by the fact that the pA2-value of prazosin, an alpha 1-antagonist, was approximately 2 log units higher than that of yohimbine, an alpha 2-antagonist. However, pA2-values of four quinazolines (prazosin, bunazosin, SM911 and SM2470) and two yohimbine alkaloids (yohimbine and corynanthine) were significantly lower in the rabbit dilator muscle than in rabbit aortic strips. Two imidazoline antagonists (phentolamine and tolazoline) and a phenethanolamine (labetalol) acted on the alpha 1-adrenoceptors in the two tissues nonselectively. These results suggest that alpha 1-adrenoceptors in the rabbit dilator muscle and aortic strips may not be identical and that both selective and nonselective antagonists which act on these receptor sites exist.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1986

Antagonistic effect of KC-404, a new anti-asthmatic agent, on leukotriene D4-induced contractile responses in isolated guinea pig smooth muscles.

The inhibitory effects of KC-404, a novel clinically available anti-asthmatic drug, on leukotriene(LT) D4-, LTC4-, histamine- and acetylcholine(ACh)-induced contractile responses in isolated guinea pig lung parenchymal, tracheal and ileal longitudinal strips were compared using an organ bath system. In lung parenchyma, KC-404 antagonized LTD4 in a competitive fashion, whereas it antagonized histamine noncompetitively. The pA2 value against LTD4 was 7.39. KC-404 hardly antagonized LTC4 and ACh. A ranked order of potency estimated from its minimum effective concentrations (MEC) was LTD4 greater than histamine greater than LTC4 greater than ACh. In trachea, KC-404 antagonized LTC4 and LTD4 in a competitive fashion, while it antagonized histamine noncompetitively. The pA2 values against LTC4 and LTD4 were 5.99 and 6.51, respectively. KC-404 hardly antagonized ACh. A ranked order of the potency estimated from MEC was LTD4 greater than LTC4 greater than histamine greater than ACh. The pA2 values of KC-404 against LTD4 in lung parenchyma and trachea were little or not altered, while its inhibitory effect on histamine-induced contraction in trachea was markedly diminished by the pretreatment of tissues with indomethacin. In ileum, KC-404 noncompetitively antagonized all of the agonists used. A ranked order of the potency estimated from pD2 values was LTD4 divided by LTC4 greater than histamine greater than ACh. These results suggest that KC-404 is a selective antagonist of LTD4 and that it might interact with LTD4 receptor in airway smooth muscles but not in ileum. Another possibility that the drug might interact with LTD4 specific excitation-contraction coupling mechanism was also discussed.

Acetylcholine↗
PubMed1986

Nitro compounds (isosorbide dinitrate, 5-isosorbide mononitrate and glyceryl trinitrate) on the femoral vein and femoral artery.

In organ bath studies, the selectivity of isolated femoral vein and artery of rabbit to isosorbide dinitrate (ISDN), 5-isosorbide mononitrate (ISMN), major metabolite of ISDN, and glyceryl trinitrate (GTN) was compared. The femoral vein and artery contracted by norepinephrine were relaxed by all the nitro compounds dose-dependently. Potency order was GTN greater than ISDN greater than ISMN. The maximum inhibitory responses to the nitrocompounds and their pIC50 values (negative logarithms of doses to induce the 50% response) were greater in the femoral vein than in the femoral artery. For ISMN a 3 times greater sensitivity of femoral vein than of femoral artery was found.

Animals↗
PubMed1986

Anti-leukotriene D4 action of a new anti-asthmatic drug (KC-404) on the guinea-pig isolated trachea.

Anti-asthmatic drug, KC-404, inhibited specifically spontaneous contraction and leukotriene (LT) D4-induced contraction of guinea-pig trachea. Relaxation of spontaneous contraction by KC-404 was reduced by the treatment of the guinea-pig trachea with a cyclooxygenase inhibitor, flurbiprofen. Some parallel shift of the concentration-action curve of LTD4 by KC-404 was still observed in the presence of flurbiprofen. Specific binding of [3H]LTD4 to the microsomal fraction of guinea-pig trachea was partially inhibited by KC-404. These results suggest that the relaxing action of trachea of KC-404 is due to the interference of interaction between LTD4 and its receptor and to the product(s) via cyclooxygenase pathway.

Animals↗
PubMed1986

Selectivity of cerebral vasodilators on basilar arteries.

Ca-antagonistic activities of cerebral vasodilators, nicardipine and 1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100) were tested on basilar and renal arteries, thoracic aorta and portal vein of rabbit, and rat vas deferens. Both the cerebral vasodilators used herein had a selectivity to basilar arteries. The selectivity to the basilar arteries is considered to be one of the factors in deciding the pharmacological property of the cerebral vasodilators.

Animals↗
PubMed1986

Actions of 4-(2-hydroxy-3-[(1-methyl-3-phenylpropyl)amino]propoxy) benzeneacetamide (KF4317) and labetalol on alpha- and beta-adrenoceptors.

Blocking activities of alpha- and beta-adrenoceptors by 4-(2-hydroxy-3-[(1-methyl-3-phenylpropyl)amino]propoxy)benzeneacetamide (KF4317) were tested on the isolated muscles, compared with the action of labetalol. In blocking the beta 1-adrenoceptor, KF4317 was almost as active as labetalol. KF4317 was about 1/10th as potent as labetalol in blocking the beta 2-receptor. KF4317 was beta 1-adrenoceptor selective. KF4317 was about 1/50th as potent as labetalol in blocking the alpha 1-receptor. KF4317 did not interact with the alpha 2-adrenoceptor in concentrations up to 10(-5) M. The present results indicate that KF4317 is a selective beta 1- and alpha 1-adrenoceptor blocker, though the alpha 1-adrenoceptor blocking action is weak.

Animals↗
PubMed1986

Interactions of muscarinic drugs with their receptors in single cells of guinea-pig taenia caecum.

Single cells were prepared from the guinea-pig taenia caecum and used for the study of drug-receptor interactions. The cells showed a graded response to carbachol, the dose response curve being shifted in a parallel fashion by atropine, indicating a competitive antagonism. The pA2-value of atropine was in agreement with that estimated using the intact tissue. [3H]QNB (quinuclidinyl benzilate) combined with the single cells, the Scatchard plot yielding a straight line. The dissociation constant of QNB was similar to values estimated in other membrane preparations. The apparent dissociation constants of cholinergic drugs estimated from inhibition of the specific binding of [3H]QNB (0.20 nM) to the single cells by the cholinergic drugs were also in agreement with the values in other membrane preparations. The results indicate that the single smooth muscle cells are useful for the study of drug-receptor interactions.

Animals↗