Search PubMed⌕ Search

Biomedical subjects

D M Jackson

Publications and source records attributed to D M Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1988

Enhancement by a single dose of reserpine (plus alpha methyl-p-tyrosine) of the central stimulatory effects evoked by dopamine D-1 and D-2 agonists in the mouse.

With the advent of selective dopamine D-1 and D-2 agonists such as SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine HCl) and quinpirole (LY171555, trans-4,4a,5,6,7,8a,9-octahydro-5-propyl-2H-pyrazolo [3,4-g]quinoline), it has become possible to examine the functional role of the two dopamine receptor subtypes as well as their interrelationship. In the present study, we pretreated mice with the granule-depleting agent reserpine (5 mg/kg sc) and tested the mice from 4 h to 10 days later. In all the studies, each mouse also received an injection of the dopamine synthesis inhibitor alpha methyl-p-tyrosine (200 mg/kg ip) 1 h before agonist challenge. Where the reserpine was given 2 or more days before testing, a second dose of reserpine was given 4 h before agonist challenge. While producing no significant locomotor stimulation 4 h after reserpine, SKF38393 produced a dose-dependent increase in coordinated locomotion 24 h and 3 days after the reserpine. Likewise, quinpirole itself produced no significant alteration in activity at 4 h, but significantly increased activity at 24 h and 3 days. The new selective D-1 agonist CY208-243 ((-)-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo [4,3-ab] phenanthridine), unlike SKF38393, produced some increase in activity 4 h after reserpine, but much greater activity was seen 1 and 3 days after reserpine. The enhancement with SKF38393, CY208-243 and quinpirole was most marked 3 days after the reserpine. The behavioural stimulation produced by the mixed D1/D2 agonist apomorphine was also greater 3 days after reserpine pretreatment than after 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

The effect of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid-induced cough in dogs.

1. The effects of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid-induced cough have been studied in conscious tracheostomised dogs. 2. Nedocromil sodium (approximately 15 mg given as an aerosol) and codeine phosphate (5 mg kg-1, i.v.) significantly increased the time to the first cough when dogs were challenged with citric acid aerosol. The mean number of coughs in the initial period of coughing fell after treatment of dogs with nedocromil sodium or with codeine phosphate, but this reduction in mean cough number was not statistically significant. 3. Neither sodium cromoglycate (approximately 15 mg given as an aerosol) nor saline had significant effect on a citric acid challenge. 4. It is concluded that nedocromil sodium, but not sodium cromoglycate, possesses an anti-tussive action that may result from inhibition of sensory nerve activity in the lung. Nedocromil sodium may prove useful in the treatment of unproductive cough in situations where the use of a centrally-acting antitussive is undesirable.

Animals↗
PubMed1988

Opioid modulation of non-cholinergic neural bronchoconstriction in guinea-pig in vivo.

1. Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non-cholinergic (NC) neural bronchoconstriction in guinea-pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea-pig. 2. Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea-pigs which was reduced by atropine (1 mg kg-1), but the NC component was unaffected by hexamethonium (10 mg kg-1). 3. NC bronchoconstriction was reduced by morphine in a dose-dependent manner (ED50 = 132 micrograms kg-1 with a maximal inhibition of 79 +/- 2.1% at 1 mg kg-1). Yohimbine (0.5 mg kg-1) did not alter the inhibitory effect of morphine (1 mg kg-1). 4. The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg-1) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg-1) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. 5. The selective mu-opioid receptor agonist Tyr-(D-Ala)-Gly-(N-Me-Phe)-Glyol (DAGOL) was significantly more potent than morphine with an ED50 of 5.4 micrograms kg-1 and complete inhibition at 100 micrograms kg-1. The delta-agonist Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE) was less potent than DAGOL with an ED50 of 28 micrograms kg-1 and a maximal inhibition of only 50 +/- 5% at 100 micrograms kg-1. The delta-agonist Tyr4D-Pen)-Gly-Phe-D-Pen) (DPDPE) was less potent than DAGOL with an ED5o of 28pgkg-1 and a maximal inhibition of only 50 + 5% at lOOPgkg- . The Kappa-receptor agonist, U-50,488H had no inhibitory effect on the NC bronchoconstrictor response. 6. The bronchoconstrictor responses to exogenous substance P (25 pgkg- 1) or acetylcholine (25 pg kg- 1) were unaffected by morphine (500 pg kg- 1). 7. We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on mu-opioid receptors localized to sensory nerve endings in the airway.

Acetylcholine↗
PubMed1988

Dopamine-mediated behaviours produced in naive mice by bromocriptine plus SKF 38393.

The ability of bromocriptine and SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) to produce some dopamine-mediated behaviours has been assessed in mice. Soon after injection, SKF38393 produced moderate increases in grooming and sniffing which were not very intense, while bromocriptine (with or without SKF38393) inhibited all grooming behaviour. Bromocriptine alone also depressed rearing and sniffing in the first hour and SKF38393 alone was without effect on rearing, but the combination produced a marked increase in the incidence of both rearing and sniffing, both of which behaviours appeared to be stereotyped. When bromocriptine-induced locomotor stimulation was peaking about 3 h after injection, as measured in automated activity cages in previous studies, there was an increase in sniffing and rearing, the incidence of which was unaffected by the addition of SKF38393, perhaps due to the shorter duration of action of SKF38393 than of bromocriptine. The data indicate that the D-1 agonist SKF38393 can qualitatively and quantitatively alter the behavioural spectrum produced by the D-2 agonist bromocriptine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Acute transient SO2-induced airway hyperreactivity: effects of nedocromil sodium.

The effect of nedocromil sodium given as an aerosol on the immediate lung hyperreactivity and lung inflammation caused by a 2-h exposure to 400 ppm SO2 has been studied in dogs. Exposure to SO2 caused an immediate increase in bronchial responsiveness to histamine aerosol that lasted for approximately 2 h. The total number of cells recovered by bronchial lavage increased postexposure. Initially this increase was caused by epithelial cells (0.25 and 1 h) and later by neutrophils (1, 2, 3, and 4 h). There was no significant change in the numbers of lymphocytes, macrophages, eosinophils, goblet cells, or mast cells in the lavages. Nedocromil sodium (approximately 8 mg) given as a nebulized aerosol before and after SO2 exposure prevented the increase in lung reactivity and attenuated the increase in the total number of cells (epithelial cells and neutrophils) in the lung lavages for the 4 h after exposure. Nedocromil sodium did not affect the reactivity of normal dogs to histamine aerosol. Nedocromil sodium appears to act as an anti-inflammatory agent in this model of lung inflammation, preventing an increase in lung reactivity and reducing cell infiltration. The mechanism of action of nedocromil sodium in this model is unknown.

Animals↗
PubMed1987

Bromocriptine-induced locomotor stimulation in mice is modulated by dopamine D-1 receptors.

Mice were pretreated with reserpine plus alpha-methyl-p-tyrosine (10 mg/kg plus 200 mg/kg). One hour later they were administered the selective dopamine D-2 agonist bromocriptine or vehicle. Three hours after the bromocriptine, mice were challenged with the selective D-1 agonist SKF 38393, and locomotor activity was measured each 5 min for three hours. Neither bromocriptine nor SKF 38393 produced significant stimulation. The combination, however, produced a dose-dependent and coordinated increase in activity. If the bromocriptine was given only one hour before the SKF 38393 challenge (i.e., three hours after the reserpine plus alpha-methyl-p-tyrosine), no interaction was seen. In naive mice, when SKF 38393 and bromocriptine were administered together, the locomotor response to bromocriptine was quantitatively and qualitatively altered. The initial depressant response to bromocriptine was shortened, producing a more rapid onset of the stimulant response. In one experiment, the maximal activity induced by bromocriptine was increased by SKF 38393. The ability of SKF 38393 to alter the locomotor stimulant effect of bromocriptine in naive mice was blocked by their pretreatment with the selective D-1 antagonist, SCH 23390. The data indicate that the locomotor stimulant effects of bromocriptine are modulated by D1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Differential electrophysiological effects of 3-PPP and its enantiomers on dopamine autoreceptors and postsynaptic receptors.

The activities of substantia nigra pars compacta dopamine and globus pallidus neurons have been examined following the systemic administration of ( +/- )-3-PPP and the enantiomers of 3-PPP to investigate the relative effects of these putative dopamine agonists on dopamine autoreceptors and postsynaptic dopamine receptors. ( +/- )-3-PPP inhibited the firing rates of 7 out of 10 dopamine cells completely (ED50 = 0.18 +/- 0.06 mg/kg) but caused no consistent or significant alterations in the firing rates of globus pallidus neurons, exhibiting an apparent selectivity for the dopamine D-2 autoreceptors. However, (+)-3-PPP effectively inhibited the activity of all dopamine neurons studied (ED50 = 0.09 +/- 0.03 mg/kg) and, like d-amphetamine, apomorphine and other dopamine agonists, significantly stimulated pallidal activity. (-)-3-PPP was less effective at inhibiting dopamine cell activity; it had no effect on firing rates of pallidal cells when given alone, but it reversed the pallidal rate increases induced by (+)-3-PPP and also blocked the rate increases induced by systemically administered apomorphine. The results show that (-)-3-PPP, given systemically, acts as a partial agonist in the substantia nigra pars compacta and as an antagonist on postsynaptic dopamine receptors. These effects of (-)-3-PPP appear to account for the apparent dopamine autoreceptor selectivity demonstrated by racemic 3-PPP and further indicate that the autoreceptors and postsynaptic dopamine receptors may be differentially affected by a drug with mixed agonist/antagonist properties. These conclusions are consistent with those obtained from other techniques and support the idea that the effects of dopamine agonists on the activity of dopamine neurons and globus pallidus cells can provide an indication of the relative selectivity of these drugs for pre- or postsynaptic dopamine receptors.

Action Potentials↗
PubMed1986

Bromocriptine induces marked locomotor stimulation in dopamine-depleted mice when D-1 dopamine receptors are stimulated with SKF38393.

In mice pretreated with reserpine plus alpha-methyl-p-tyrosine, neither the D-2 selective agonist bromocriptine, nor the D-1 selective agonist SKF38393, produced any measurable increase in locomotion in mice. However, the combination of the two agonists produced a marked and dose-dependent increase in co-ordinated locomotor activity. In mice with their dopamine stores and dopamine synthesis intact, SKF38393 was inactive by itself, but significantly enhanced the stimulant effect produced by bromocriptine. The data suggest that bromocriptine requires concomitant stimulation of D-1 receptors for the full expression of its behavioural stimulant effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Bromocriptine enhances the behavioural effects of apomorphine and dopamine after systemic or intracerebral injection in rats.

The ergot alkaloid bromocriptine, given intraperitoneally produced dose-dependent, long-lasting stereotyped behaviour in rats which was partly antagonised by the injection of trifluoperazine into the caudate nucleus. The stereotyped behaviour produced by apomorphine (s.c.) in both naïve and catecholamine-depleted rats was significantly enhanced by prior treatment with bromocriptine (i.p.). The bilateral application of bromocriptine (2.5-40 micrograms/side in either 0.5% tartaric acid or 50% propylene glycol aqueous vehicles) to the nucleus accumbens (NAC) of rats had no effect on locomotion over a 12 hr period after injection. In contrast, another ergot alkaloid, ergometrine, dissolved in the propylene glycol vehicle, and dopamine (DA) dissolved in either of the vehicles or in saline, produced marked stimulation of locomotion. As well as being inactive after direct application to the nucleus accumbens, bromocriptine (10-160 micrograms/side) did not induce stereotyped behaviour after bilateral injection into the caudate nucleus. However, the local application of bromocriptine (10 micrograms/side) to the nucleus accumbens, while itself inactive, significantly enhanced the locomotor stimulant effect of DA (5 micrograms/side) applied to the same nucleus. The data suggest that bromocriptine is able to enhance the effects of agonists such as DA and apomorphine at DA receptors, even under conditions where bromocriptine itself is inactive.

Animals↗
PubMed1986

A behavioral role for enkephalins in regulating locomotor activity in the insect Leucophaea maderae: evidence for high affinity kappa-like opioid binding sites.

D'-Ala-2 met-5-enkephalinamide application to the cerebral ganglia of Leucophaea maderae results in a decrease in locomotor activity. The opiate antagonist, naloxone, can block this effect as well as the depressant effect of morphine on locomotor activity. D-Ala-2,leu-5-enkephalinamide and dynorphin enhance locomotor activity following their topical application to the cerebral ganglia. This effect also can be antagonized by concomitant naloxone treatment. Benzomorphans were the most potent ligands tested in their ability to displace [3H]D'-ala-2,met-5-enkephalinamide whereas mu and delta ligands were by comparison less potent. These results suggest the presence of kappa-like opioid receptors in Leucophaea cerebral ganglia. The kappa ligands also are potent in enhancing locomotor activity in addition to being weakly antagonized by naloxone. Again, these results indicate the presence of multiple-opiate receptor types in invertebrates.

Animals↗
PubMed1986

Maternal awareness.

Explore the source record for details and available documents.

Anesthesia, Inhalation↗
PubMed1986

Expression of melanoma-associated antigens by normal and neurofibroma Schwann cells.

The cell surface antigen distribution on traumatic neuroma Schwann cells and neurofibroma Schwann-like cells was characterized using monoclonal antibodies that define melanoma-associated antigens. Immunofluorescence staining of cultured cells, immunoprecipitation of radioiodinated antigens from cells placed in short-term cultures, and immunoperoxidase staining of frozen tissue sections revealed most of the melanoma-associated antigens tested on traumatic neuroma and neurofibroma Schwann cells and on fetal and adult femoral nerve. The cross-reactivity of the antibodies with neural cells may reflect the common neural crest embryological origin of Schwann cells and melanocytes. Cell sorter analysis of neurofibroma cells using a monoclonal antibody directed against the melanoma nerve growth factor receptor resulted in cell cultures highly enriched for Schwann-like cells which may bear the genetic defect responsible for neurofibromatosis. The antigen detected by this monoclonal antibody is the neurofibroma nerve growth factor receptor and the antibody was a potent inhibitor of nerve growth factor binding to neurofibroma cells.

Antibodies, Monoclonal↗
PubMed1986

Monkeys infected with Ascaris suum (a new in vivo model of airway disease): protective effect of nedocromil sodium and sodium cromoglycate against bronchial antigen challenge.

The experimental infection of Macaca arctoides monkeys with the nematode parasite Ascaris suum induces an IgE-mediated immediate hypersensitivity reaction similar to that seen in naturally sensitive animals. In the present study, the effects of inhalation of Ascaris suum antigen on lung function in infected monkeys were investigated, together with the effects of aerosolized nedocromil sodium and sodium cromoglycate (each 4 mg) given 5 min prior to antigen challenge. Ascaris suum-infected Macaca arctoides monkeys bronchoconstricted when they inhaled Ascaris antigen, maximal effects being seen 2-5 min after antigen inhalation. This bronchoconstriction was inhibited by nedocromil sodium pretreatment but not by sodium cromoglycate. This animal model therefore provides a new experimental model of airways disease.

Animals↗
PubMed1985

Isolation and amino terminal sequencing of a novel melanoma-associated antigen.

The biochemical characteristics are described for a melanoma-associated glycoprotein antigen, whose expression depends on stage of tumor progression and melanocytic differentiation. This antigen, identified using a monoclonal antibody which specifically stains melanoma cells in immunoperoxidase assay of fixed tissue sections, is synthesized as a 30,000-Da precursor and then processed to a 30,000- to 60,000-Da sialylated glycoprotein. Two-dimensional gel electrophoresis of the antigen resolved more than 20 forms, heterogeneous in both charge and molecular weight. The kinetics of post-translational processing, the sensitivity of processing to tunicamycin, and the molecular weight of the oligosaccharide chains indicate that the oligosaccharides are N-linked. Amino acid sequencing of the antigen purified by immunoaffinity chromatography and by high-pressure liquid chromatography or polyacrylamide gel electrophoresis allowed the assignment of the first 20 acids.

Amino Acid Sequence↗
PubMed1985

Properties of a Ca2+ and Mg2+ stimulated ATPase in the rat caudate nucleus.

Adenosine triphosphatase (ATPase) activity which could be stimulated maximally by either Ca2+ or Mg2+ was identified in a synaptosomal fraction from rat brain caudate nucleus. The thermodynamic properties of the Ca2+ and Mg2+ stimulated enzymes were similar to each other. Oligomycin, sodium azide and dinitrophenol had no significant inhibitory effects on stimulation by either cation. In vitro incubation of the ATPase with cis- or trans-flupenthixol, chlorpromazine or trifluoperazine, but not with haloperidol, significantly inhibited stimulation by either cation. The DA receptor agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) inhibited stimulation of the enzyme by either cation, while d-amphetamine, SKF 38393, pergolide and LY-171555 had no significant effects. Nomifensine at 10(-3) M inhibited the cation stimulation by about 33%. In vivo administration of dopamine (DA) receptor antagonists (haloperidol, cis- and trans-flupenthixol, spiperone, chlorpromazine and trifluoperazine) and the agonist apomorphine neither inhibited nor stimulated ATPase activity. It appears from these data that the ATPase activity is not under DA receptor modulation. In addition, our tentative conclusion is that one enzyme is involved, because both Ca2+ and Mg2+ produced similar maximal stimulations, the activities as a function of temperature were similar, the enzyme could not be further stimulated with Ca2+ after maximal stimulation by Mg2+ (and vice versa), and the behaviour of the ATPase activity to all drugs tested was similar.

Animals↗