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C M Stubbs

Publications and source records attributed to C M Stubbs.

10 recordsLinked to original sources
PubMed1996

Dopamine D3 receptors in the basal ganglia of the common marmoset and following MPTP and L-DOPA treatment.

The distribution of the dopamine D3 receptor was studied by receptor autoradiography using [3H]7-OH-DPAT in striatal and extrastriatal brain regions of the common marmoset (Callithrix jacchus). Saturation studies demonstrated that [3H]7-OH-DPAT bound with similar affinity to different regions of marmoset brain. In normal marmosets, specific [3H]7-OH-DPAT binding was found in both striatal and extrastriatal regions. Very high levels of specific [3H]7-OH-DPAT binding were detected in the islands of Calleja and nucleus accumbens but in addition high levels of binding were detected in rostral caudate nucleus and putamen. In common marmosets treated with the selective nigral neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the levels of specific [3H]7-OH-DPAT binding in striatal and extrastriatal regions were not different to those in normal animals. Chronic treatment of MPTP-treated marmosets with L-DOPA/ carbidopa did not alter the levels of specific [3H]7-OH-DPAT binding in any brain region. These results demonstrate that in common marmosets D3 receptors are located in both striatal and limbic regions. The receptor density is not altered by dopaminergic denervation or by chronic L-DOPA administration. The D3 receptor may, therefore, be important in both the therapeutic and adverse effects of drugs used to treat Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Neurokinin-induced changes in pial artery diameter in the anaesthetized guinea-pig.

1. The effects of selective neurokinin agents on pial artery diameter, measured with an on-line image analyser, have been studied in anaesthetized guinea-pigs in order to characterize the neurokinin receptors present on pial arteries. 2. Perivascular injection of either substance P (0.01-1 microM) or the selective NK1 receptor agonists, substance P methyl ester (SPOMe, 0.01-1 microM) and GR73632 (0.1 microM), increased pial artery diameter. 3. In contrast, the selective NK2 receptor agonist, GR64349 (1 microM), produced a small vasoconstriction while the NK3 receptor-selective agonist, senktide (1 microM) was inactive. 4. Co-administration of GR82334 (1 microM), a selective NK1 receptor antagonist, inhibited the vasodilatation produced by SPOMe (0.1 microM) but not that caused by calcitonin gene-related peptide (CGRP, 0.01 microM). 5. The results are consistent with an involvement of NK1 receptors in the neurokinin-induced increase in guinea-pig pial artery diameter.

Animals↗
PubMed1992

Effect of sumatriptan, a selective 5-HT1-like receptor agonist, on pial vessel diameter in anaesthetised cats.

The action of sumatriptan, a selective 5-HT1-like receptor agonist that is effective for the acute treatment of migraine, was compared on pial vessel diameter following perivascular or intravenous administration to anaesthetised cats. Sumatriptan (0.01-10 microM), when microinjected perivascularly, caused a decrease in pial artery diameter (maximum change of -19 +/- 9%; mean +/- SD) but had no effect on the diameter of pial veins. Sumatriptan (1 microM)-induced pial artery vasoconstriction was unaffected by coadministration of ketanserin (1 microM) or ondansetron (1 microM) but was significantly (p less than 0.01) attenuated by methiothepin (1 microM). Intravenous infusion of a clinically effective dose of sumatriptan (64 micrograms/kg/10 min) caused selective carotid vasoconstriction (22 +/- 6% increase in carotid vascular resistance with little or no change in blood pressure or heart rate) and no change in pial artery diameter, although sumatriptan (1 microM) administered perivascularly in these animals before and after the infusion caused pial artery vasoconstriction. These results demonstrate that perivascularly administered sumatriptan causes pial artery vasoconstriction via activation of 5-HT1-like receptors. However, intravenously administered sumatriptan does not cause pial artery vasoconstriction, which suggests that sumatriptan does not readily penetrate the cerebrovascular intima.

Animals↗
PubMed1992

Characterization of the receptor mediating relaxation to substance P in canine middle cerebral artery: no evidence for involvement of substance P in neurogenically mediated relaxation.

1. The aim of this study was to characterize the neurokinin receptor which mediates relaxation of dog isolated middle cerebral artery by the use of selective agonists and antagonists and to establish whether substance P is involved in the neurogenically mediated relaxant response in this vessel. 2. Substance P caused concentration-related, endothelium-dependent relaxations of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha. The selective NK1 receptor agonists, GR73632 and substance P methyl ester (SPOMe), also caused relaxation with similar maximum effects to those of substance P. GR73632 and SPOMe were approximately 20 times and 6 times less potent respectively than substance P. The selective NK2 and NK3 receptor agonists, GR64349 and senktide, were only weakly active in causing relaxation being at least 425 times and 245 times less potent respectively than substance P. 3. The selective NK1 receptor antagonist, GR82334, was a potent, specific, competitive antagonist of the relaxant effects of substance P. In contrast, the selective NK2 receptor antagonist, R396 (10 microM) had no effect on the response to substance P. 4. Electrical field stimulation of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha, caused neurogenically mediated, non-adrenergic non-cholinergic (NANC) relaxations. These NANC relaxations were unaffected by endothelium removal, GR82334 (10 microM) or by capsaicin (10 microM) treatment. However, the nitric oxide synthesis inhibitor, L-NG-monomethyl arginine methyl ester (L-NMMA) (100 microM) markedly attenuated the response to electrical stimulation. 5. These results suggest that substance P causes relaxation of dog isolated middle cerebral artery via activation of NK1 receptors. However, substance P does not appear to be involved in NANC neurotransmission. In contrast, the marked inhibitory effect of L-NMMA on NANC relaxations implicates nitric oxide in NANC neurotransmission in this vessel.

Animals↗
PubMed1991

BMY 7378 is an agonist at 5-HT1A receptors mediating hypotension and renal sympatho-inhibition in anaesthetised cats.

The putative 5-HT1A receptor antagonist BMY 7378 (3-100 micrograms.kg-1 i.v.) caused reductions in blood pressure, heart rate and efferent renal nerve activity in anaesthetised cats. Similar effects were produced by the selective 5-HT1A receptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT 1-10 micrograms.kg-1 i.v.). The sympatho-inhibitory effects of BMY 7378 and 8-OH-DPAT, but not those of clonidine were reversed by the non-selective 5-HT1A receptor antagonist, spipirone (1 mg.kg-1 i.v.). It is concluded that BMY 7378 is an agonist at 5-HT1A receptors mediating hypotension and renal sympatho-inhibition in anaesthetised cats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Vasodilator effect of 8-OH-DPAT in the isolated perfused mesenteric bed of the rat: no evidence for involvement of 5-HT1A receptors.

1. In the isolated perfused mesenteric bed of the rat, bolus administration or infusion of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT; bolus 0.3-90 nmoles, infusion 0.03-30 microM) caused dose-related decreases in phenylephrine-induced tone. 2. These vasodilator responses were not modified by the 5-HT1A receptor antagonists BMY7378 (0.3 microM) or cyanopindolol (0.1 microM). 3. A number of compounds, having a range of affinities for 5-HT1A receptors, were tested in the mesentery and also for antagonist activity at alpha 1-adrenoceptors in the rabbit isolated aorta. 4. The potency of 8-OH-DPAT, flesinoxan, ipsapirone, sumatriptan and phentolamine, at decreasing phenylephrine-induced tone in the mesentery correlated closely with antagonist potency at alpha 1-adrenoceptors (r = 0.99) but not with affinity at 5-HT1A binding sites (r = -0.2). 5. It is concluded that the vasodilator effect of 8-OH-DPAT in the mesenteric bed of the rat most probably reflects alpha 1-adrenoceptor antagonist activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

The effects of flurbiprofen, aspirin, cimetidine, and antacids on the gastric and duodenal mucosa of normal volunteers. An endoscopic and photographic study.

This 7-day, single blind, randomized endoscopic tolerance study compared daily doses of 100, 150 and 200 mg flurbiprofen with 2600 mg aspirin. After seven days the flurbiprofen 100 and 150 mg groups had significantly less gastric irritation than the flurbiprofen 200 mg and aspirin groups. Flurbiprofen showed a linear dose-response relationship with respect to gastric injury and serum drug levels. Four subjects each on aspirin and flurbiprofen with the most severe injuries continued on their medications plus cimetidine and antacids for four more weeks. Both drug groups showed clinical improvement in the gastroduodenal area. In conclusion, flurbiprofen and aspirin therapy can be tolerated in the presence of gastroduodenal irritation by concomitantly administering cimetidine and antacids.

Adult↗
PubMed1973

Arthur Kidd.

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History, 20th Century↗