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Biomedical subjects

H O Collier

Publications and source records attributed to H O Collier.

At least 37 records · Page 2Linked to original sources
PubMed1980

Cellular site of opiate dependence.

Experiments on whole animals, guinea pig isolated ileum, individual neurones in situ and cultured neuroblastoma--glioma hybrid cells indicate that opiate dependence and associated tolerance develop within neurones bearing specific opiate receptors (opiate-sensitive neurones). The essential change appears to be an hypertrophy of the cyclic AMP system, in response to inhibition by opiate of a neuronal adenylate cyclase.

Action Potentials↗
PubMed1980

Prostaglandin receptors in the airways.

An analysis of the effects of some natural prostaglandins and of synthetic analogues with more selective actions points to the existence of several receptors for prostaglandins in the airways. Three effects have been studied: the contraction and relaxation of bronchial smooth muscle in vitro and the cough elicited by inhalation of prostaglandin aerosols by the conscious cat. From the rank orders of potency of a group of prostaglandins and analogues, from tachyphylaxis induced by continued exposure to a single species and from antagonism by indomethacin or mefenamic acid, three prostaglandin receptors have been distinguished: (1) for contraction (chi receptor) and (2) for relaxation (psi receptor) of bronchial smooth muscle, and (3) for cough (omega receptor). The natural prostaglandins tested stimulated to different extents each of these three receptors; but synthetic analogues with selective actions on only one or two receptors were identified. It seems likely that (1) prostaglandins or thromboxanes not yet tested will interact with these receptors, (2) other receptors for these substances may be distinguished in the airways, (3) the receptors so far distinguished may also be found in other sites, and (4) the receptor categories described may be subdivisible.

Animals↗
PubMed1980

2-decarboxy-2-hydroxymethyl prostaglandin E1 (TR4161), a prostaglandin bronchodilator of low tracheobronchial irritancy.

2-Decarboxy 2-hydroxymethyl prostaglandin E1 (TR4161) relaxed isolated quinea-pig trachea with about double and relaxed human isolated bronchial muscle with about one half the potency of PGE1. In conscious restrained cats an aerosol of TR4161 was about 100-1000 times less active than PGE1 in inducing tracheobronchial irritation. When given intravenously or by aerosol to the anaesthetised spontaneously breathing guinea-pig, TR4161 was approximately equipotent with PGE1 in inhibiting histamine-induced bronchoconstriction and in reducing basal inherent tone. The onset and duration of the bronchodilator effects of TR4161 administered intravenously, however, were significantly longer than those of PGE1. In conscious quinea-pigs, TR4161 by aerosol was approximately three times more potent than PGE1 in preventing histamine-induced convulsions, whereas only TR4161 was active in this test system when the test drugs were administered orally. These observations indicate that TR4161 might be therapeutically useful as a non-irritant prostaglandin bronchoidilator in conditions of airway obstruction.

Administration, Oral↗
PubMed1980

Specific receptors for prostaglandins in airways.

The relative bronchomotor activities of prostaglandins (PG) E1, E2, F2 alpha, F2 beta and I2 and of three synthetic E prostaglandin analogues (TR4161, TR4367 and TR4752) were determined on a large number of isolated preparations of guinea-pig trachea and human bronchial muscle. Each prostaglandin was capable of eliciting both contraction and relaxation, the relative incidence of these responses partly depending on concentration. TR4161 was a virtually pure relaxant; TR4367 was virtually devoid of bronchomotor activity; and TR4752 was a potent relaxant, devoid of contractant activity. The results also provided distinct rank orders of approximate potency for contraction and relaxation. Tachyphylaxis to the relaxant activities of PGE1 and TR4752 confirmed the underlying contractant activity of the two natural E prostaglandins. Antagonism with a high dose of indomethacin of the contractant actions of PGE1, PGE2 and PGF2 alpha confirmed the presence of relaxant activities in each. Inhaled aerosols of the same natural and synthetic prostaglandins were evaluated for irritant activity on the airways, using the cough response of the restrained conscious cat. All of them, except TR4161, elicited severe coughing. The rank order of potencies for irritancy differed from those for tracheobronchial contractant and relaxant activities. These findings suggest that the three responses studied arise from the activation of three distinct PG receptors in the airways. We propose the terms chi (contractant), psi (relaxant) and omega (irritant) for these putative receptors for prostaglandins or possibly other prostanoids.

Animals↗
PubMed1980

Receptors for E and F prostaglandins in airways.

Determination of dose/response relationships for E and F PGs in guinea pig trachea and human bronchial muscle in vitro indicates that mixed contractant and relaxant activities are present in different proportions in each PG. Further analysis of these effects, using (a) tachyphylaxis to individual PGs and (b) indomethacin as a PG antagonist, argues that two PG receptors exist on tracheobronchial muscle. Activation of one of these (chi receptor) leads to contraction, and of the other (psi receptor) to relaxation. Individual E and F PGs interact with these two receptors in different proportions. A third potent effect of PGs on airways is to elicit cough. That PGF2 alpha elicits cough but has very little relaxant activity, whereas certain PG analogs and PGE1 elicit cough but possess either no bronchomotor or almost entirely relaxant activity, argues that a third receptor (omega) exists, the activation of which elicits cough.

Animals↗
PubMed1979

Paracetamol potentiates acetylsalicylate in inhibiting prostaglandin synthesis.

Lower concentrations of paracetamol stimulated, but a higher concentration inhibited prostaglandin synthesis by bull seminal vesicle homogenate in the absence of added co-factors. Admixed with acetylsalicylate or indomethacin, paracetamol strongly potentiated the inhibition of prostaglandin synthesis in vesicle homogenate, and weakly potentiated inhibition in rat gastric fundus strip. We propose that, by acting as a phenolic co-factor, paracetamol stimulates prostaglandin synthesis and thus renders the cyclo-oxygenase more vulnerable to acetylsalicylate or indomethacin.

Acetaminophen↗
PubMed1979

Mechanism of quasi-morphine withdrawal behaviour induced by methylxanthines.

Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome (QMWS) in opiate-naive rats, five were effective in a dose-related way. These, in descending order of potency, were IBMX, ICI-63197, RO-201724, theophylline and caffeine. Their potencies in inducing a QMWS correlated significantly (P less than 0.05) with those in inhibiting low Km cyclic AMP phosphodiesterase of rat brain homogenate. There was no correlation with potencies in inhibiting cyclic GMP phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Tracheobronchial irritancy of inhaled prostaglandins in the conscious cat.

A novel test was developed to measure the tracheobronchial irritant activity of inhaled prostaglandins. Conscious restrained cats were challenged with separate aerosols of PGE1, PGF2alpha, acetylcholine or isoprenaline. All of the aerosols except isoprenaline caused coughing in a concentration related manner. Tolerance developed very quickly to the tracheobronchial irritation and lasted 1-2 days for PGE1 and less than 1 day for PGF2alpha and acetylcholine. When a 3 day interval between each aerosol challenge was used, PGF2alpha was approximately 700 times more potent than acetylcholine as a tracheobronchial irritant. The highest PGE1 aerosol concentration (500microgram/ml) also caused sedation, diarrhoea and salivation. This test probably provides a useful method for evaluating the tracheobronchial irritant activity of potential prostaglandin bronchodilator analogues and for investigating the mechanism of action of prostaglandin induced tracheobronchial irritancy.

Acetylcholine↗
PubMed1978

Prostaglandins and opioids.

In guinea-pig small intestine, rat brain in vitro and neuroblastomaXglioma hybrid cells, opioids specifically inhibit the action of E prostaglandins. In the whole rat, E prostaglandins, administered centrally, antagonize the antinociceptive action of morphine. E prostaglandins also antangonize the induction of opioid tolerant/dependence. In turn, tolerance/dependent preparations respond with added intensity to E prostaglandins. The antagonism between opioids and E prostaglandins does not occur at the opioid receptor; but, certainly in some preparations and probably in others, this antagonism occurs at the coupling or catalytic unit of a neuronal adenylate cyclase that opioids inhibit and E prostaglandins stimulate. The proposition that antagonism of E prostaglandin at appropriate neurons in the brain is part of the natural mechanism of opioid analgesia remains possible, but unproven, and is worth continued investigation.

Analgesics↗