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Biomedical subjects

M G Gillan

Publications and source records attributed to M G Gillan.

24 records · Page 2Linked to original sources
PubMed1980

Comparison of the binding characteristics of tritiated opiates and opioid peptides.

1 Binding assays on homogenates of guinea-pig brain showed that the maximal number of binding sites was different tritiated ligands interacting with the opiate receptors. 2 At 25 degrees C the binding capacity of morphine or dihydromorphine was only about 3 pmol/g fresh brain whereas etorphine and D-Ala2-L-Leu5- and D-Ala2-L-Met5-enkephalin amide had capacities of 13 to 15 pmol/g brain. D-Ala2-D-Leu5-enkephalin had an intermediate capacity of about 6 pmol/g brain. 3 The binding capacities of the natural methionine- and leucine-enkephalins measured at 0 degrees C were 5 to 6 pmol/g brain. At this temperature, the binding capacity of dihydromorphine, D-Ala2-D-Leu5-enkephalin and of the two enkephalin amides was only slightly lower than at 25 degrees C. 4 In assays in which unlabelled ligand competed with the same labelled ligand, the inhibition constants (KI) were equal to or not more than twice as large as the equilibrium dissociation constant (KD) determined in saturation assays. In contrast, the KI of unlabelled dihydromorphine against [3H]-D-Ala2-D-Leu5-enkephalin or of unlabelled D-Ala2-D-Leu5-enkephalin against [3H]-dihydromorphine was about 20 times higher than the respective KD values. 5 When for a given compound the ratio of the KI value against [3H]-D-Ala2-D-Leu5-enkephalin to the KI value against [3H]-dihydromorphine (discrimination ratio) is calculated, a high value indicates selectivity in favour of the mu-receptor and a low value selectivity in favour of the delta-receptor. The most selective mu-agonist known so far is normorphine with a discrimination ratio of 70 and the most selective delta-agonist is D-Ala2-D-Leu5-enkephalin with a ratio of 0.11. The selectivity of the known antagonists is in favour of the mu-receptor, since their discrimination ratios are larger than 1, varying between 10 for naloxone and 4 for Mr 2266.

Animals↗
PubMed1980

Acute effects of morphine and opioid peptides on the motility and responses of rat colon to electrical stimulation.

1 Morphine and leucine- and methionine-enkephalins inhibited the contractile response of the pithed rat colon to electrical stimulation of the spinal motor outflows and inhibited motor responses of the isolated colon to field stimulation. 2 Morphine and the opioid peptides also had an excitatory action in the colon. In the pithed rat, opiates caused regular fluctuations in intracolonic pressure and in the isolated colon, caused regular waves of contraction. This excitatory response was produced by low concentrations of the enkephalins (2 X 10(-8) M, 2 X 10(-9) M), was stereospecific and was antagonized by naloxone. 3 Opiate-induced contractions in the isolated colon were inhibited by catecholamines, adenine nucleotides and by phosphodiesterase inhibitors. These contractions were unaffected by ergotamine and tolazoline, or by propranolol. 4 The excitatory action of opiates in the isolated colon was not antagonized and usually was potentiated by atropine, (+)-tubocurarine and hexamethonium. In the absence of opiates, these drugs also produced similar waves of contraction, which were unaffected by naloxone. 5 Opiate-induced contractions occurred in colon rendered unresponsive to 5-hydroxytryptamine (5-HT) and these contractions were potentiated by the 5-HT antagonist, lysergic acid diethylamide, which, when administered alone, caused similar contractions. The 5-HT antagonist, cyproheptadine, inhibited opiate-induced contractions but was non-specific, since it also inhibited responses of the colon to carbachol and KC1. 6 Opiate-induced contractions were unaffected by procaine and were potentiated by tetrodotoxin. Both of these drugs, when administered alone, produced waves of contractions, which were similar to those produced by opiates but were unaffected by naloxone. 7 Contractions produced in the isolated colon either by opiates, atropine or (+)-tubocurarine, or any combination of these drugs, were inhibited by field stimulation applied at the peak of a wave of contraction. This inhibitory response to field stimulation occurred at low frequencies of stimulation (less than 10 Hz), and persisted in colon from rats pretreated with reserpine to deplete, or 6-hydroxydopamine to destroy, adrenergic nerve endings. It was unaffected by guanethidine but abolished by tetrodotoxin. 8 The implications of these results are considered and it is concluded that the excitatory action of opiates in the rat colon is probably not mediated by the release of acetylcholine or 5-HT but instead, may be due either to a direct action on smooth muscle or to a presynaptic inhibitory action at a ganglionic site in a non-adrenergic inhibitory mechanism, which normally suppresses myogenic activity.

Animals↗
PubMed1979

The inhibitory effects of presynaptic alpha-adrenoceptor agonists on contractions of guinea-pig ileum and mouse vas deferens in the morphine-dependent and withdrawn states produced in vitro.

1 Isolated ilea from guinea-pigs implanted with morphine pellets were stimulated coaxially, either with or without morphine present in the bath fluid, and the longitudinal contractions recorded. 2 In the absence of morphine the inhibitory effects of the presynaptic alpha-adrenoceptor agonists, clonidine and oxymetazoline were much reduced and the dose-response curve was flat. This state of 'withdrawal' was readily reversed by morphine and levorphanol but not its inactive (+)-isomer, dextrophan. 3 The kappa-agonists, ketazocine and ethylketazocine, also restored the effects of clonidine as did the opioid peptides Tyr-D-Ala-Gly-Phe-D-Leu, acting preferentially on delta-receptors, and Tyr-D-Ala-Gly-MePhe-Met(O)-ol, acting mainly on micro-receptors. 4 The inhibitory effects of adrenaline and adenosine 3',5'-diphosphate were reduced at low but not at high concentrations. 5 In contrast, the inhibitory effect of clonidine on the electrically evoked contractions of vasa deferentia from mice implanted with morphine pellets was not abolished by the lack of morphine in the bath fluid or by addition of naloxone. 6 A possible explanation is suggested for the loss of the inhibitory effects of presynaptic alpha-adrenoceptor agonists in the withdrawn state of the dependent ileum.

Adenosine Diphosphate↗