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Biomedical subjects

J B Cheng

Publications and source records attributed to J B Cheng.

52 records · Page 3Linked to original sources
PubMed1984

Identification of leukotriene D4 receptor binding sites in guinea pig lung homogenates using [3H]leukotriene D4.

We have characterized [3H]leukotriene D4 binding to guinea pig lung homogenates. Both biphasic dissociation kinetics and curvilinear Scatchard plots indicated the presence of [3H]leukotriene high and low affinity states of the binding sites. The rank order of potency for the competition study was leukotriene C4 = leukotriene D4 greater than leukotriene E4 much greater than arachidonic acid, and for their contractile effect on lung strips was leukotriene C4 = leukotriene D4 = leukotriene E4 much greater than arachidonic acid. FPL-55712 was the only other agent tested that inhibited binding. These results suggest that binding of [3H]leukotriene D4 to the homogenate is consistent with its binding to specific leukotriene D4 receptor sites.

Animals↗
PubMed1983

GTP increases airway muscarinic antagonist binding sites: an effect regulated by Mg2+.

Using [3H]QNB, we demonstrated that GTP and Gpp(NH)p increased muscarinic receptor high affinity sites in bovine tracheal muscle preparations; however, neither the dissociation constant of [3H]QNB binding sites nor pulmonary beta-adrenergic receptor sites was altered. The GTP effect on increasing the receptor sites was relatively small (16%), sensitive (ED50 0.48 microM) and specific (Gpp(NH)p greater than GTP = GDP greater than GMP much greater than ATP). Mg2+ potentiated this increase by up to 94.8%, whereas Na+, K+ and Ca2+ had no such effect.

Animals↗
PubMed1983

Decreased sensitivity and response of isolated tracheal muscle to methacholine and histamine without changing the activity of pulmonary muscarinic receptors in the egg albumin-sensitized guinea pig.

Guinea pigs were sensitized by daily intraperitoneal injections of 100 mg of egg albumin for 3 consecutive days and sacrificed at 30-35 days after the last injection. The in vitro sensitivity and response of the sensitized tracheal muscle to methacholine and histamine were significantly less than those of littermate controls. However, there was no difference between the dissociation constants and concentrations of pulmonary muscarinic receptor binding sites of the control and sensitized guinea pigs. We conclude that subsensitivity and hyporesponsiveness to methacholine and histamine occur in the airway muscle of this guinea pig model of experimental asthma and suggest that the decreased reactivity to methacholine might be due to defects beyond the receptor.

Animals↗
PubMed1983

Pharmacological characterization of effects of nifedipine on isolated guinea-pig and rat tracheal smooth muscle.

Nifedipine, a relatively new Ca2+-channel blocking agent, has recently been shown to be effective in the treatment of exercise-induced asthma; however, the pharmacological mechanism by which it blocks bronchospasm is little understood. We have investigated and characterized its effects on the reactivity of isolated guinea-pig and rat tracheal smooth muscle. Although it (10(-8)--10(-7)M) blocked the contraction of the rat tracheal muscle to KCl and CaCl2, nifedipine (10(-7)--10(-6)M) did not significantly inhibit histamine, methacholine or serotonin-induced muscle contractions in guinea-pigs and the methacholine contraction in rats. Nifedipine produced a potent relaxation on contracted tracheal muscle. The concentration required to produce 50% relaxation on 10(-5)M histamine-precontracted guinea-pig tracheal muscle was 8.31 +/- 3.12 X 10(-9)M, and the extent of the nifedipine-induced relaxation could be modified by the baseline and active contracted tension. Nifedipine was more potent in producing the relaxation in guinea-pig tracheal muscle than isoproterenol, theophylline or verapamil. However, the time required for 50% relaxation by 3 X 10(-5)M isoproterenol was significantly less than the time for the nifedipine (3 X 10(-5)M) or verapamil (10(-4)M) effect. In addition, the Hill number of the nifedipine-induced relaxation was different from the value of the isoproterenol or verapamil effect. Our results indicate that nifedipine exerts a potent dilatory effect directly on airway muscle, and suggest that such effect could be one of its pharmacological actions on relieving bronchospasm.

Airway Resistance↗
PubMed1982

Comparison of muscarinic and beta adrenergic receptors between bovine peripheral lung and tracheal smooth muscles: a striking difference in the receptor concentration.

This study was undertaken to compare the activity of muscarinic and beta adrenergic receptors in bovine peripheral lung to the corresponding receptor activity in tracheal smooth muscle. We used [3H] quinuclidinyl benzilate (QNB) and [3H]dihydroalprenolol (DHA) to measure muscarinic and beta receptor activity, respectively. Binding to QNB and DHA at 25 degrees C was rapid, reversible, saturable and of high affinity. The order of potency for cholinergic and adrenergic agents competing for binding was compatible with muscarinic and beta 2 adrenergic potencies. We found that the concentration of muscarinic receptor binding sites was 37-fold greater in the tracheal muscle preparation (2805 +/- 309 fmol/mg protein) than in the peripheral lung preparation (76 +/- 28 fmol/mg protein). Unlike muscarinic receptors, the lung contained 8-fold higher concentration of the beta adrenergic receptors than did the tracheal muscle (1588 +/- 417 vs. 199 +/- 42 fmol/mg protein). The dissociation constant or the agonist's inhibitory constant (Ki) for either receptor binding site, however, was not significantly different between the two tissues. Furthermore, in vitro contraction studies showed that the response of tracheal muscle strips to methacholine was markedly greater than the response of peripheral lung strips, a finding consistent with the QNB binding result. The muscle but not the peripheral lung strip exhibited a relaxing response to epinephrine. Our data indicate a striking quantitative difference in muscarinic and beta adrenergic receptors between lung tissue and tracheal muscle, and that each receptor in the lung is qualitatively similar to the corresponding receptor in the muscle.

Animals↗
PubMed1982

Effects of chronic histamine and ovalbumin aerosols on pulmonary beta adrenergic receptors in sensitized guinea pigs.

Using (3H) dihydroalprenolol, we demonstrated that the concentration of pulmonary beta adrenergic receptor binding sites was lower in guinea pigs showing a marked bronchoconstrictive response to histamine and in ovalbumin-treated guinea pigs. This result suggests that the changed concentration of the pulmonary beta receptors in an animal model of asthma could be resulted from bronchoconstriction stress.

Aerosols↗
PubMed1981

Identification of beta-adrenergic receptors using [3H]dihydroalprenolol in fetal sheep heart: direct evidence of qualitative similarity to the receptors in adult sheep heart.

The fetal sheep heart responds to beta-adrenergic stimuli; however, in vivo studies show the response of the fetal heart is less than that of the adult heart. We used [3H]dihydroalprenolol (DHA) to study directly beta-adrenergic receptors in heart particulates of fetal sheep at term and adult sheep. [3H]DHA binding to fetal heart particulates was rapid, reversible (t 1/2 = 2.9 +/- 0.3 min), stereoselective, saturable (101.2 +/- 7.4 fmoles/mg protein), and of high affinity (4.8 +/- 0.4 nM). The rank order of agonists competing for [3H]DHA binding was isoproterenol (0.32 +/- 0.10 microM) greater than epinephrine (1.19 +/- 0.23 muM) approximately equal to norepinephrine (2.67 +/- 0.69 muM), which is compatible with beta 1-adrenergic potencies. [3H]DHA also bound to the adult sheep heart in a manner expected for beta 1-receptors. No difference in the binding affinity of [3H]DHA or agonists' competition was demonstrated between the fetal and adult sheep heart. Comparison of the concentration of beta-adrenergic receptors in fetal and adult hearts was confounded by the choice of the denominator for unit expression. The concentration was higher in the adult when expressed as a function of protein content or 5'-nucleotidase activity (0.52 +/- 0.07 versus 1.12 +/- 0.06). However, there was no difference when tissue weight, Na+ - K+-ATPase, or NaF-stimulated adenylate cyclase was used. Furthermore, isoproterenol-stimulated adenylate cyclase and cardiac contractile response to a threshold dose of isoproterenol were identical in the fetal and adult sheep heart. We conclude that beta-receptors can be studied with [3H]DHA in the fetal sheep heart, this receptor is qualitatively similar to the beta-receptor in the adult sheep heart, and it is unlikely that there is a difference in the concentration of beta-adrenergic receptors in fetal and adult sheep heart.

Adenylyl Cyclases↗
PubMed1980

Decreased concentration of myocardial alpha-adrenoceptors with increasing age in foetal lambs.

Using [3H]-dihydroergocryptine, we identified myocardial alpha-adrenoceptor binding sites in foetal lambs and demonstrated that the concentration of receptors decreased with increasing foetal age. The presence of the receptor in the foetus correlated with the presence of myocardial alpha-adrenergic responsiveness. However, we found neither the alpha-receptor binding site nor responsiveness to alpha-adrenoceptor stimulation in the myocardium of adult sheep.

Animals↗
PubMed1980

Glucocorticoids increase pulmonary beta-adrenergic receptors in fetal rabbit.

beta-Adrenergic agonists stimulate surfactant release and decrease fluid in lung alveoli of fetuses. Both effects are most evident toward the end of gestation. We used [3H] dihydroalprenolol (DHA) to investigate the development of pulmonary beta-adrenergic receptors in rabbit fetuses and to study the effect of glucocorticoid treatment on the beta-receptor number. In the lung particulate preparation, DHA binding was rapid, reversible, stereoselective, and of high affinity. The order of potency for adrenergic agonists in competing for DHA binding was isoproterenol > epinephrine = norepinephrine, which is typical of interactions at a beta 1-adrenergic receptor. Using DHA, we demonstrated that the concentration of pulmonary beta-receptors increased significantly between 28 and 31 days of gestation; however, there was no change in the dissociation constant during gestation. After injecting betamethasone (0.17 mg/kg, 24 hours) into rabbits at 25 days of pregnancy, we found that the concentration of pulmonary beta-receptors increased from 44.2 +/- 6.6 fmol/mg protein in untreated fetuses to 77.9 +/- 5.6 fmol/mg protein in treated fetuses. However, this treatment did not affect the DHA binding sites in the fetal rabbit heart. Maternal treatment with the T3 analogue 3,5-dimethyl-3'-isopropyl-L-thyronine (0.5-1 mg/kg) at a dosage which increased both surfactant synthesis and release did not alter pulmonary receptor concentration. Our results indicate that the concentration of pulmonary beta-adrenergic receptors increases in the fetus at term and suggest that this increase is stimulated by endogenous glucocorticoid in fetal circulation.

Animals↗
PubMed1980

Pressor response to 5-hydroxytryptamine, norepinephrine and KCi in the perfused hindquarter preparation from the spontaneously hypertensive rat.

The pressor response to 5-hydroxytryptamine (5-HT), norepinephrine (NE), and KCI was studied in the blood- and Ringer's- perfused hindquarters of the spontaneously hypertensive rat (SHR) and the Kyoto normotensive Wistar rat in two age groups: 8 to 10 weeks and 6 to 8 months. In both preparations, the response to 5-HT, NE and KCI was greater in the young and old SHRs than in the age-matched normotensive Wistar rats. The enhanced responsiveness to 5-HT in old SHRs was of greater magnitude than that to NE or KCI, whereas in young SHRs the enhanced responsiveness to the three pressor agents was of similar magnitude. This appears to be due in part to a greater reduction in responsiveness to NE and KCI than to 5-HT as the animal becomes older. Enhanced responsiveness to 5-HT also occurs in the renal hypertensive rat. However, there was no difference in responsiveness to low doses of NE or KCI in the renal hypertensive rat. The response to 5-HT in the old SHR was blocked by methysergide but was not affected by phentolamine, isoproterenol or nitroglycerin. In the old SHR made hypotensive by occlusion of the abdominal aorta for a duration of 3 to 5 weeks, the responsiveness to all three pressor agents was reduced but was most marked for 5-HT. These latter results suggest that blood pressure per se contributes to the enhanced responsiveness to NE, KCI and, to a greater extent, 5-HT.

Animals↗
PubMed1977

Reactivity of isolated human cerebral arteries to biogenic amines.

Serotonin (5-HT), histamine, norepinephrine, methoxamine and isoproterenol caused dose-dependent contraction of human cerebral arteries. The potency of 5-HT was greater among test agents in the basilar arteries, whereas it was equivalent to that of norepinephrine in human anterior, middle and posterior cerebral arteries. Acetylcholine and carbachol (10(-9)-10(-5) M) caused a negligible response in human cerebral arteries. Contractile response to 5-HT was greater in the distal rather than middle portion of the human basilar arteries while this order was reversed in the response to norepinephrine. Tyramine (10(-4) M) caused tonic contraction and nicotine (10(-4) M) and electrical transmural stimulation produced phasic contraction of arteries which were antagonized by adrenergic blocking agents. Adenine nucleotides failed to cause relaxation and only high concentration of adenosine caused a minute relaxation. However, papaverine and nitroglycerin caused marked relaxation. These results suggest that adrenergic mechanism may play a role in the regulation of vascular tone in human cerebral arteries.

Acetylcholine↗
PubMed1976

Differences in effect of 6-hydroxydopamine on the right and left atria from guinea-pig.

The effect of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) treatment was studied on guinea-pig atria. 6-OHDA treatment significantly reduced the positive inotropic effect of nicotine and tyramine on the left atrium, while similar treatment on the intact atria and the right atrium showed a decreased response to tyramine but not to nicotine. After 6-OHDA treatment the left atrium but not the right atrium showed supersensitivity to noradrenaline. The 6-OHDA induced reduction of catecholamine content and noradrenaline uptake was less effective on the right atrium in comparison to the left atrium and ventricles. After 6-OHDA treatment, tissue catecholamine fluorescence disappeared from all tissue layers of the left atrium but the number of specific fluorescent nerve terminals of the right atrium was only slightly decreased. These results indicate that adrenergic mechanisms of the right atrium exhibit higher resistance to sympathectomy by 6-OHDA than the left atrium.

Animals↗
PubMedDate not supplied

Vascular relaxation in the spontaneously hypertensive rat.

The relaxation of thoracic and abdominal aortae of the spontaneously hypertensive rat (SHR) during prehypertensive (3--5 week old) and hypertensive (12--16 and 22--25 week old) stages was compared to that of matched normotensive Wistar rats (NWRs). In the thoracic aorta, the relaxation response to isoproterenol, acetylcholine, Mg2+, Mn2+, Co2+, and La3+ was less in both prehypertensive and hypertensive SHRs than in the matched NWRs; however, such difference was not evident in the abdominal aorta. Similarly, the relaxing effect of nitroglycerin and papaverine was not different in the aorta preparations of the SHR and NWR. After chronic reserpine treatment of the prehypertensive and hypertensive SHRs, the thoracic aorta still showed less relaxation in response to the aforementioned agents. Isoproterenol, but not other agents tested, produced less relaxation in the thoracic aorta from the renal hypertensive rat than from the control. Our results suggest that the decreased relaxation of the SHR thoracic aorta is not a consequence of hypertension and that the defect in the SHR thoracic aorta cannot be generalized to other vascular beds.

Acetylcholine↗
PubMedDate not supplied

Fetal pulmonary beta-adrenergic receptors: characterization in the human and in vitro modulation by glucocorticoids in the rabbit.

At least two developmental responses necessary to prepare the fetal lung to serve as a gas-exchange organ, the release of surface-active material and the reabsorption of alveolar water, can be stimulated by beta-adrenergic agonists. The sensitivity of these responses increases dramatically in late gestation. beta-Adrenergic receptors can be identified by radioligand binding and are present in human fetal lung as early as 16 weeks of gestation. The temporal relationship of the increases in both pulmonary beta-receptors and plasma-free cortisol in the fetal rabbit during gestation suggests that endogenous glucocorticoids may cause increased concentration of pulmonary beta-receptors. Treatment of pregnant rabbits at 24 or 25 days of gestation results in precocious increases in both fetal lung beta-receptors and agonist-specific, high-affinity binding. The increase in receptor concentration with glucocorticoid is not dependent on other endocrine response inasmuch as 0.1 microM dexamethasone increases beta-receptor concentrations at 24 and 48 hours of incubation in cultures of fetal rabbit lung organ. This effect of glucocorticoid to increase beta-receptor concentration and high-affinity binding may explain the increased fetal pulmonary beta-adrenergic response at term and may be responsible in part for the reduction in neonatal respiratory syndrome seen after antenatal glucocorticoid therapy.

Adenylyl Cyclases↗