Biomedical subjects

C J Moody

Publications and source records attributed to C J Moody.

27 records · Page 2Linked to original sources

PubMed1990

Functional and autoradiographic evidence for endothelin 1 receptors on human and rat cardiac myocytes. Comparison with single smooth muscle cells.

This study aimed to determine whether receptors for endothelin were present on the cardiac myocyte as well as on vascular smooth muscle cells. Low- and high-resolution autoradiography was performed using 125I-endothelin 1 on intact rat myocardium and samples of human ventricle obtained from explanted hearts at the time of transplant. In addition to specific binding to the smooth muscle of the blood vessel lumen, there was considerable binding associated with cardiac myocytes. To discover whether there was any functional correlate for this binding, muscle cells were isolated enzymatically from human and rat ventricle and from rat femoral artery, and their contractile characteristics were studied. Single cardiac cells were superfused with physiological saline at 32 degrees C, and their length change was displayed continuously on a chart recorder. Endothelin 1 had a pronounced effect on shortening in both rat and human myocytes. The contraction amplitude was approximately doubled in both cases, from 4.1 +/- 0.8% cell length to 8.1 +/- 1.3% for rat (mean +/- SEM, n = 9, p less than 0.001), and from 2.1 +/- 0.5% to 4.0 +/- 0.5% in human (n = 10, p less than 0.001). In rat, the magnitude of the effect was comparable to that of the alpha-adrenoceptor agonist phenylephrine. The maximum contraction amplitude of the human cells, produced by raising extracellular calcium to greater than 10 mM, was 11.4 +/- 1.1% cell length (n = 9), significantly greater than that produced by endothelin (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Stretch reflex oscillations and essential tremor.

Using a computer-controlled torque motor and manipulandum, 50 ms torque pulses and 70 second trains of binary pseudorandom torque disturbances were applied to the wrists of 10 adult controls and 22 patients with essential tremor in order to study the interaction between mechanically-induced stretch-reflex oscillations and essential tremor. These two oscillations were separated by applying inertial and spring loads to the wrist. There was no evidence of increased or unstable stretch-reflex activity in the essential tremor patients, and stretch-reflex latencies did not correlate with the frequency of essential tremor. Essential tremor and mechanically-induced stretch-reflex oscillations are separate phenomena capable of complex interaction.

Adult↗

PubMed1986

Caldesmon: a calmodulin-binding actin-regulatory protein.

The protein caldesmon, originally isolated from smooth muscle tissue where it is the most abundant calmodulin-binding protein, has since been shown to have a wide distribution in actin- and myosin- containing cells where it is localized in sub-cellular structures concerned with motility, shape changes and exo- or endo-cytosis. Caldesmon is believed to be an actin- regulatory protein, and binds with high affinity to actin or actin-tropomyosin. Caldesmon inhibits the activation by actin-tropomyosin of myosin MgATPase activity, and the inhibition can be reversed by Ca2+.calmodulin. The binding of caldesmon to smooth muscle proteins has been studied in detail, enabling a model to be constructed which could account for the observed Ca2+ regulation of smooth muscle thin filaments. The abundance of caldesmon, and the Ca2+-regulation of its activity via calmodulin, mean that it is potentially an important intracellular regulator of processes such as smooth muscle contraction, cell motility and secretion.

Actins↗

PubMed1985

Bundling of actin filaments by aorta caldesmon is not related to its regulatory function.

Ca2+-sensitive thin filaments from vascular smooth muscle were disassembled into their constituent proteins, actin, tropomyosin and caldesmon. Caldesmon bound to both actin and to actin-tropomyosin and inhibited actin-tropomyosin activation of skeletal muscle myosin MgATPase. It also promoted the aggregation of actin or actin-tropomyosin into parallel aligned bundles. Quantitative electron microscopy measurements showed that with 1.1 microM actin-tropomyosin, 1.6 +/- 0.5% (n = 3) of the filaments were in bundles. At 0.073 microM, caldesmon inhibited MgATPase activity by 50%, whereas bundling was 3.0 +/- 1.3% (n = 4). At 0.37 microM caldesmon, MgATPase inhibition was 83% while 28.1 +/- 6.9% (n = 4) of filaments were in bundles. Experiments at 4.4 microM in which MgATPase and bundling were measured in the same samples gave similar results. Small bundles of 2-3 filaments showed the most frequent occurrence at 1.1 microM actin. At 4.4 microM actin the most common bundle size was 3-5 filaments, with the occasional occurrence of large bundles consisting of up to 120 filaments. The incidence of bundling was the same in the presence and absence of tropomyosin. Thus caldesmon can induce the formation of actin bundles but this property bears no relationship to its inhibition of MgATPase activity.

Actins↗

PubMed1984

Stimulation of P1-purinoceptors by ATP depends partly on its conversion to AMP and adenosine and partly on direct action.

The effects of degradative enzymes and enzyme inhibitors were examined on the inhibitory actions of adenosine, AMP and ATP on atrial muscle and on the cholinergic responses of the ileum to transmural stimulation of the guinea-pig, in order to determine whether ATP responses are mediated by its breakdown products, AMP and adenosine. In both the atria and the ileum, adenosine deaminase reduced responses to ATP, although when combined with 5'-nucleotidase it had no further effect. In the atrium, the 5'-nucleotidase inhibitor, alpha,beta-methylene ADP (APCP), had no effect on its own, but prevented the potentiating effect of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) on responses to ATP. In the ileum, EHNA had no effect, but APCP potentiated responses to ATP. The enzyme 5'-AMP deaminase was shown to have a non-specific inhibitory effect on purine responses in both preparations. It is concluded for both preparations, that (1) the inhibitory responses to ATP are partly mediated by AMP and adenosine following the ectoenzymatic breakdown of ATP, and partly mediated by ATP itself, and (2) that AMP as well as adenosine can act directly on P1-purinoceptors. It is suggested that of the two breakdown products of ATP, AMP and adenosine, a larger proportion of the response is mediated by AMP in the ileum, whereas adenosine is the major mediator in the atrium.

5'-Nucleotidase↗

PubMed1982

The design of a new group of angiotensin-converting enzyme inhibitors.

Using X-ray and NMR data relating to the conformation of the antihypertensive, angiotensin-converting enzyme inhibitor, captopril, and structure--activity relationships of analogues, it has been possible to postulate with the aid of computer graphics, the orientation of the three functions, the thiol, the terminal carboxyl and the carbonyl group which are involved in binding to the enzyme. Bicyclic mimetics of captopril, with related arrays of these functions, have been designed and synthesized. Compounds with the closest approximation to the array in captopril are the most active inhibitors of angiotensin converting enzyme, in vitro.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1982

Evidence for the presence of P1-purinoceptors on cholinergic nerve terminals in the guinea-pig ileum.

The inhibitory effects of adenosine, ATP, 5'-adenylyl methylene diphosphonate (beta, gamma-meATP) and adenosine 5'-alpha, beta-methylene triphosphonate (alpha, beta-meATP) were compared on the cholinergic twitch responses to transmural stimulation of the guinea-pig ileum. Adenosine, ATP and beta, gamma-meATP reduced the twitch responses in a concentration dependent manner. Theophylline antagonized and dipyridamole potentiated the inhibitory responses to adenosine, ATP and beta, gamma-meATP. Inhibitory responses to alpha, beta-meATP were usually preceded by an enhancement in twitch height. Contractions of the unstimulated ileum to alpha, beta-meATP were blocked by atropine and tetrodotoxin while those elicited by ATP were unaffected, which suggests that the initial excitatory effects of alpha, beta-meATP may be due to its ability to release ACh from cholinergic nerve terminals. Use of high pressure liquid chromatography and bioluminescence assay techniques demonstrated the ability of the tissue to degrade ATP and beta, gamma-meATP and, at a much slower rate, alpha, beta-meATP. Inhibitory responses to ATP, AMP and beta, gamma-meATP were reduced by adenosine deaminase, which also abolished responses to adenosine. 5'-AMP deaminase abolished responses to AMP and adenosine, and reduced those to ATP and beta, gamma-meATP. The results suggest that the inhibitory effect of ATP on cholinergic neurotransmission is due to its rapid breakdown to AMP or adenosine, which act on prejunctional P1-purinoceptors.

Adenosine↗

PubMed1982

Evidence for stereospecificity of the P1-purinoceptor.

1 The effects of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), 2-chloroadenosine, 2-azidoadenosine, and their L-enantiomers were examined on driven left atria, trachea and transmurally stimulated ileum of the guinea-pig. 2 In each tissue the order of potency of the D-enantiomers for producing inhibitory effects was NECA greater than 2-chloroadenosine greater than 2-azidoadenosine greater than adenosine. 3 The log concentration-response curve of each agonist was shifted to the right in the presence of the P1-purinoceptor antagonist, theophylline. 4 Dipyridamole, which blocks adenosine uptake, potentiated the effects of adenosine but not those of the D-enantiomers of adenosine analogues. 5 The greater potency of the adenosine analogues therefore, is at least partly due to their resistance to tissue uptake and subsequent enzymatic destruction. 6 The L-enantiomers of adenosine and its analogues did not produce inhibitory responses in the driven left atria or transmurally stimulated ileum. At high concentrations relaxations of the tracheal muscle were obtained, with the potency series L-NECA greater than 2-chloro-L-adenosine greater than 2-azido-L-adenosine greater than L-adenosine. 7 It is concluded that the postsynaptic P1-purinoceptors in the guinea-pig atria and trachea and the presynaptic P1-purinoceptors on cholinergic nerve terminals in guinea-pig ileum are stereospecific for the D-enantiomers of adenosine and its analogues.

2-Chloroadenosine↗

PubMed1981

8-phenyltheophylline: a potent P1-purinoceptor antagonist.

8-Phenyltheophylline was more potent than theophylline in antagonizing the inhibitory effects of adenosine in guinea-pig driven left atrium, rabbit basilar artery and electrically stimulated guinea-pig ileum preparations. In guinea-pig atrium and ileum, the antagonism of adenosine responses by the methylxanthines is of a competitive nature, but in rabbit basilar artery it does not appear to be so. In all three preparations, the effects of theophylline and 8-phenyltheophylline could be reversed by washing. It is concluded that 8-phenyltheophylline is a more potent P1-purinoceptor antagonist than theophylline.

Adenosine↗