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Biomedical subjects

H C Cheng

Publications and source records attributed to H C Cheng.

At least 109 records · Page 6Linked to original sources
PubMed1982

Phospholipase A2 activity in the rat uterus during early pregnancy.

The activity of phospholipase A2 (PLA2), which provides free arachidonic acid and is widely accepted as the rate-limiting step in the biosynthesis of prostaglandins (PGs), was determined by radioisotopic method in the rat uterus on days 1 through 6 of pregnancy. Serum levels of progesterone (P4) and estradiol-17 beta (E2) were also determined by radioimmunoassay. Uterine PLA2 activity peaked in the morning of day 4 of pregnancy (15.85 +/- 2.44 nmol/h/mg protein). While the activity was low (5.78 +/- 0.80) in the morning of day 5 of pregnancy, a small peak (9.12 +/- 1.62) was noticed in the afternoon of day 5. Serum P4 levels, as expected, showed a gradual increase with the advancement of pregnancy, but the serum E2 levels in the same samples were undetectable under our assay conditions. The results are discussed in relation to the hormonal control of PLA2 activity and hence PG production in the uterus during early pregnancy.

Animals↗
PubMed1982

A kinetic study of the antihistaminic effect of terfenadine.

Kinetics of the antihistaminic effect of alpha-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) were examined in the isolated guinea pig ileum and spirally cut tracheal strip preparations. In the isolated guinea pig ileum, terfenadine produced a parallel or competitive shift (3.16 X 10(-8) and 10(-7) mol/l) as well as a nonparallel or unsurmountable shift (3.16 X 10(-7) and 10(-6) mol/l) of the histamine dose response curves. Using the dose ratio test, it was concluded that terfenadine competes at the same receptors as chlorpheniramine, namely, the histamine H1-receptors. The antihistaminic effects of terfenadine, both the competitive and unsurmountable effects, were difficult to reverse by washout techniques whereas the nonspecific effects (against acetylcholine and barium chloride) could be readily washed out. The unsurmountable antagonism of histamine by terfenadine may result from a slow dissociation of terfenadine from the histamine H1-receptor. When terfenadine (2 mg/kg) or chlorpheniramine (2 mg/kg) was administered systemically, either orally or intraperitoneally, to guinea pigs and the antihistaminic effect assessed in vitro (isolated ileal strips and tracheal strips) terfenadine consistently produced a longer duration of action than chlorpheniramine. It is concluded that terfenadine is a potent, selective histamine H1-receptor antagonist; the kinetics of association/dissociation of terfenadine with histamine H1-receptors may account for the long-lasting antihistaminic effect in various animal models.

Animals↗
PubMed1981

Endocrinological effects of strong 60-Hz electric fields on rats.

Adult male rats were exposed or sham-exposed to 60-Hz electric fields without spark discharges, ozone, or significant levels of other secondary variables. No effects were observed on body weights or plasma hormone levels after 30 days of exposure at an effective field strength of 68 kV/m. After 120 days of exposure (effective field strength = 64 kV/m, effects were inconsistent, with significant reductions in body weight and plasma levels of follicle-stimulating hormone and corticosterone occurring in one replicate experiment but not in the other. Plasma testosterone levels were significantly reduced after 120 days of exposure in one experiment, with a similar but not statistically significant reduction in a replicate experiment. Weanling rats, exposed or sham-exposed in electric fields with an effective field strength of 80 kV/m from 20 to 56 days of age, exhibited identical or closely similar growth trends in body and organ weights. Hormone levels in exposed and sham-exposed groups were also similar. However, there was an apparent phase shift between the two groups in the cyclic variations of concentrations of hormones at different stages of development, particularly with respect to follicle-stimulating hormone and corticosterone. We concluded that 60-Hz electric fields may bring about subtle changes in the endocrine system of rats, and that these changes may be related to alterations in episodic rhythms.

Animals↗
PubMed1981

Salicylamide derivatives related to medroxalol with alpha- and beta-adrenergic antagonist and antihypertension activity.

Analogues of medroxalol (1) were prepared in which the carboxamide function, the phenolic hydroxy group, and the aralkylamine side chain were modified. N-alkyl-substituted amide analogues of 1 showed diminishing beta-blocking activity with increasing steric bulk of the alkyl group. This allowed the conclusion that deactivation of the phenolic hydroxy group of 1 by the carbonyl group of the amide function is responsible for the beta-adrenergic antagonistic properties of 1. This conclusion was strengthened by the finding that the phenolic O-methyl analogue 5-[2-[[3-(1,3-benzodioxol-5-yl)-1-methylpropyl]amino]-1hydroxyethyl]-2-methoxybenzamide (13) was found to have enhanced beta-adrenergic blocking activity. The finding that 13 also had decreased alpha-blocking activity compared to 1 indicated that the phenolic hydroxy group of 1 enhances alpha-adrenergic antagonism. The finding that 1 and 13 showed such a large difference in relative alpha- to beta-blocking potency while exhibiting approximately equal antihypertensive activity in spontaneously hypertensive rats was surprising. In indicated that pharmacologic properties other than alpha- and beta-adrenergic blockade may contribute to the antihypertensive activity of medroxalol. One of the analogues in which the aralkylamine side chain of 1 was replaced by a fragment of a known alpha-adrenergic receptor blocker, 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]benzamide (22), showed an interesting pharmacologic profile of potential therapeutic usefulness.

Adrenergic alpha-Antagonists↗
PubMed1981

Effects of clonidine on gastric acid secretion in the rat.

The effect of clonidine on gastric acid secretion was studied in the pylorus ligated stomach (Shay test) and in the perfused stomach of the rat. Clonidine produced biphasic (inhibitory and stimulatory) effects on gastric acid secretion. In the Shay test, clonidine produced only an inhibitory effect on spontaneous gastric acid secretion in a dose-dependent manner (ED50 = 0.042 mg/kg, intraduodenal administration). In the perfused stomach, clonidine in a dose range of 0.625 to 5 mg/kg i.p. slightly increased acid secretion. The secretion, induced by 5 mg/kg of clonidine, was antagonized by cimetidine (10 mg/kg i.p.) but was not affected by phentolamine. Clonidine, 1.25 mg/kg i.p., a dose which had only a slight stimulatory effect, enhanced histamine- and bethanechol-induced secretion. The enhancement of bethanechol-induced secretion was blocked by pretreatment with cimetidine, suggesting histamine H2 receptor stimulation by clonidine. After i.p. (1.25 mg/kg) or intracerebroventricular (i.c.v., 20 and 40 micrograms/kg) administration, clonidine antagonized 2-deoxy-D-glucose-induced acid secretion. Clonidine also inhibited secretion induced by vagal stimulation in anesthetized, vagi-sectioned rats. These results suggest that clonidine had both central and peripheral sites of action. The inhibitory effect on secretion induced by vagal stimulation was blocked by phentolamine (alpha-1 and alpha-2 adrenergic receptor blocker) but not by labetalol (which blocks alpha-1 but not alpha-2 receptors). It is proposed that the inhibitory effect of clonidine is due to its effect on presynaptic alpha-2 adrenergic receptors located on the postganglionic vagal fibers to the stomach. In summary, these data suggest that clonidine inhibited gastric acid secretion by both a central and a peripheral mechanism. As the dose was increased, clonidine also stimulated acid secretion by a stimulation of histamine H2 receptors.

Animals↗
PubMed1980

Effect of RMI 81968, a combined alpha- and beta-adrenergic receptor blocking agent, on histamine-induced bronchoconstriction in the dog.

The interaction of propranolol and RMI 81968 on histamine-induced bronchoconstriction was studied in the anesthetized dog using the respiratory overflow technique of Konzett and Rössler. Propranolol, 3 and 10 mumol/kg i.v., enhanced histamine-induced bronchoconstriction. In contrast, RMI 81968, at 10 or 30 mumol/kg i.v., had no effect in this test. It is believed that the alpha-receptor blocking component of RMI 81968 prevents the bronchoconstriction induced by beta-adrenergic receptor blockade. The results of this study suggest that RMI 81968 is less likely than propranolol to produce bronchoconstriction in asthmatic patients.

Adrenergic alpha-Antagonists↗
PubMed1979

Cutaneous vascular histamine H1 and H2 receptors in the guinea-pig: the histamine skin wheal as a cutaneous vascular model.

The roles of histamine H1 and H2 receptors in histamine skin wheals were studied in the guinea-pig. Intradermal injections of histamine, 0.125--2 micrograms/0.1 ml, produced wheals in a dose dependent manner. Pyrilamine maleate (3.2 mg/kg p.o., pretreatment for 1 hour) produced a dose dependent shift of the histamine wheal dose-response curve to the right in a parallel fashion. Metiamide, 3, 10 or 30 mg/kg p.o., had no effect on the histamine dose-response curve. However, a combination of metiamide (10 or 30 mg/kg) and pyrilamine (3.2 mg/kg) further increased the effect of pyrilamine. It is concluded that both H1 and H2 receptors are involved in histamine-induced wheals in the guinea-pig.

Animals↗
PubMed1977

Evidence for macromolecular synthesis in stimulation of the estrogen synthesizing system of the immature rat ovary by PMS.

Exposure of immature rat ovaries to pregnant mare's serum gonadotropin (PMS) results in a prompt increase in testosterone and progesterone output but synthesis of estradiol (E2) increases only after a lag period of several hours. Actinomycin D (Act-D) given with PMS did not inhibit testosterone or progesterone production but the estrogenic response was prevented. Delay in administration of the Act-D until 12 hr after PMS resulted in a transient increase in E2 secretion lasting less than 12 hrs. When Act-D was given 12, 16 or 20 hrs after PMS, and ovarian steroid production measured by a one hr incubation, no inhibition of progesterone, testosterone or E2 was found; the synthesis of the latter two steroids was increased by the drug. Cycloheximide, on the other hand, was most effective at inhibiting testosterone and E2 production when it was given at 12 hrs; the drug was progressively less effective in lowering production of these steroids when it was given at 16 or 20 hrs. Cycloheximide did not alter progesterone production unless it was given at the same time as PMS. The results are consistent with the view that the induction of the estrogen synthesizing system of the immature rat ovary by gonadotropin involves, during the first 12 hrs, production of a material sensitive to Act-D inhibition (mRNA?) and then production of a material sensitive to cycloheximide inhibition (protein-enzymes?). The continued production of both of these materials appears to require the continual presence of gonadotropin.

Animals↗
PubMed1977

Relationships between the chemical structure and pharmacological activities of D(-)S-and L(+)R-tropinoylcholines at cholinergic sites.

D(-)S-and L(+)R-tropinoylcholines were synthesized and their antagonisms to acetylcholine (ACh) were studied at muscarinic receptors (guinea-pig longitudinal ileal muscle), acetylcholinesterase (AChE) and pseudocholinesterase (ChE). Tropinoylcholines were reversible competitive antagonists at muscarinic receptors. D(-)S-tropinoylcholine exhibited a higher affinity as an antagonist at muscarinic receptors than the L(+)R-isomer. ONE MOLECULE OF THE ANTAGONIST COMPETES WITH ONE MOLECULE OF THE AGONIST AT EACH MUSCARINIC RECEPTOR SITE. Tropinoylcholines were competitive inhibitors of AChE. L(+)R-tropinoylcholine exhibited a lower K1 and a higher affinity for AChE. Therefore, muscarinic receptors were stereospecific for the D-configuration, whereas AChE was stereospecific forthe L-configuration of tropinoylcholine. Tropinoylcholines were week agonist at nicotinic receptors (frog rectus abdominis); they were substrates of ChE at low concentrations, but they inhibited ChE partially at high concentrations. L(+)R-tropinoylcholine had a lower apparent Km and a higher affinity than its isomer. Therefore, the esteratic site of ChE is possible stereospecific for the L-configuration of tropinoylcholine. Both tropinoylcholines were mixed inhibitors (competitive and noncompetitive) of ACh hydrolysis by ChE. The results imply that the tropinoylcholines interact at a second site as well as the esteratic site.

Acetylcholine↗
PubMed1976

Dopaminergic activity of some apomorphine analogs.

The dopaminergic activity of ten apomorphine analogs was studied in rats lesioned unilaterally with 6-hydroxydopamine in the nigro-striatal system. Of these ten compounds, N,N-dimethyl-5,6-dihydroxy-2-amino-tetralin (M-7), N-methyl-5,6-dihydroxy-2-aminotetralin (M-8) and N,N-dimethyl-4,5-dihydroxy-2-aminoindan (DDAI) exhibited potent dopaminergic stimulant activity by causing the rat to turn to the unoperated side. The turning behavior of apomorphine, M-7, DDAI and d-amphetamine were antagonized by haloperidol. M-7 and DDAI also induced pecking in pigeons and their effects were also blocked by haloperidol. It is concluded that M-7, M-8 and DDAI are direct acting central dopaminergic agents.

Animals↗
PubMed1976

Anticholinergic activities of D(-)R- and L(+)S-mandeloylcholines.

The nature of the antagonism of the D(-)R- and L(+)S-mandeloylcholines to acetylcholine (ACh) was investigated at the muscarinic receptors of the guinea-pig ileal longitudinal muscle. The nature of the inhibition of acetylcholinesterase (AChE) and serum cholinesterase (ChE) by the mandeloylcholines was also investigated. Both optical isomers of mandeloylcholine were reversible competitive antagonists of ACh at the muscarinic receptors. One molecule of mandeloylcholine combined with one receptor. The apparent affinities (1/KB, where KB = dissociation constant) of the mandeloylcholines were in the following order: homatropine greater than D(-)R-mandeloylcholine greater than DL(+/-)RS-mandeloylcholines = L(+)S-mandeloylcholine. Therefore, the mandeloylcholines were stereoselective for muscarinic receptors. The mandeloylcholines were (mixed) reversible inhibitors (competitive and noncompetitive) of ACh hydrolysis by AChE. There was no significant difference between the apparent K1 values of the mandeloylcholines in the inhibition of AChE. The mandeloylcholines were mixed reversible inhibitors (competitive and noncompetitive) of ChE. D(-)R-mandeloylcholine had a higher apparent K1 than its isomer.

Animals↗