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P B Bradley

Publications and source records attributed to P B Bradley.

At least 19 recordsLinked to original sources
PubMed1986

Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine.

As a result of controversy in the literature regarding the classification and nomenclature of functional receptors for 5-hydroxytryptamine (5-HT), a framework for classification is proposed. The formulation of these proposals has only been made possible by the recent advent of new drug tools. It is considered that there are three main types of 5-HT receptor, two of which have been well characterised pharmacologically, using selective antagonists, and which it is proposed to name 5-HT2 and 5-HT3. These two groups broadly encompass the "D" and "M" receptors, respectively, which Gaddum identified in the guinea-pig ileum (Gaddum and Picarelli, 1957). The 5-HT2 receptor, which mediates a variety of actions of 5-HT, has been definitively shown to correlate with the 5-HT2 binding site in the brain. No binding studies in brain tissue have yet been published with radiolabelled ligands specific for 5-HT3 receptors. A number of other actions of 5-HT appear to be mediated via receptors distinct from 5-HT2 or 5-HT3 receptors. Since selective antagonists are not yet available, these receptors cannot be definitively characterised, although in many cases they do have some similarities with 5-HT1 binding sites, which are a heterogeneous entity. Criteria are proposed for tentatively classifying these receptors as "5-HT1-like" (Table 1). Definitive characterisation of these receptors will await the identification of specific antagonists. This classification of 5-HT receptors into three main groups (Table 1) is based largely, but not exclusively, on data from studies in isolated peripheral tissues where definitive classification is possible. However, it is believed that this working classification will be relevant to functional responses to 5-HT in the central nervous system.

Animals↗
PubMed1986

Evidence for the existence of 5-hydroxytryptamine receptors, which are not of the 5-HT2 type, mediating contraction of rabbit isolated basilar artery.

In the rabbit isolated basilar artery the contractile action of 5-hydroxytryptamine (5-HT) was little affected by high concentrations of ketanserin (1.0 X 10(-6) M) indicating that 5-HT-receptors other than those of the 5-HT2-type were involved. The contractile action of 5-HT was mimicked by methysergide and 5-carboxamidotryptamine (5-CT) with equipotent concentration ratios (5-HT = 1) of about 22 and 0.6 respectively. This profile is characteristic of that in the dog saphenous vein which contains a 5-HT receptor type that may be described as '5-HT1-like'.

Animals↗
PubMed1985

Histamine-induced excitation of spontaneously active medullary neurones in the rat brain is mediated by H2-receptors. A microiontophoretic study using H1- and H2-agonists and antagonists.

The effects of histamine, applied by microiontophoresis onto spontaneously-active medullary neurones were investigated in the rat. Histamine caused current-dependent excitation of these neurones, an action that is at variance with previous studies in the cat. The nature of the receptor mediating these effects was examined using a number of agonists with differing potencies at peripheral H1- and H2-receptors. The precursor of histamine, L-histidine and the metabolite, N-telemethylhistamine did not mimic the effects of histamine while the H2-agonist, 4-methylhistamine caused similar but weaker excitation. The extent of excitations produced by the H1-agonists, 2-pyridylethylamine, 2-methylhistamine and 2-thiazolylethylamine could be related to their activity at H2-receptors. Metiamide was ineffective in antagonising responses to histamine and related agonists as was mepyramine. The H2-antagonist ranitidine, however, proved a good antagonist of responses to histamine and the H1- and H2-agonists, despite an unrelated excitatory action which may be linked to inhibition of cholinesterase. It is concluded that the excitatory effects of microiontophoretically-applied histamine and the agonists on medullary neurones in the rat is probably a result of activation of H2-receptors.

Animals↗
PubMed1985

Tryptamine-induced vasoconstrictor responses in rat caudal arteries are mediated predominantly via 5-hydroxytryptamine receptors.

It has been suggested that tryptamine can stimulate specific receptors distinct from those for 5-hydroxytryptamine (5-HT). We have examined this possibility in the rat isolated caudal artery, paying particular attention to the involvement of monoamine oxidase metabolism and alpha-adrenoceptors, two factors that can complicate the quantification of antagonist potencies at 5-HT receptors. 5-HT and tryptamine were agonists over the concentration-ranges 3.0 X 10(-8) - 3.0 X 10(-5) mol l-1 and 1.0 X 10(-6) - 3.0 X 10(-4) mol l-1 respectively. The sensitivity of the caudal artery to tryptamine was increased by about 44 fold in the presence of iproniazid (5.0 X 10(-5) mol l-1) and about 17 fold in the presence of pargyline (1.0 X 10(-5) mol l-1), while responses to 5-HT and methoxamine were unaffected. In the absence of iproniazid, ketanserin and methysergide were potent antagonists of responses to 5-HT with pA2 values of 9.08 and 9.11 and slopes of the Schild regressions of 1.15 and 1.00 respectively. However, against tryptamine the antagonists were weaker such that pA2 values were similar to those against 5-HT but the slopes of the Schild regressions were 0.47 and 0.47. In the presence of iproniazid (or pargyline), the 5-HT antagonists were more potent against tryptamine such that the pA2 values and the slopes of the Schild regressions were not significantly different from those against 5-HT. Phentolamine was a weak antagonist of responses to both 5-HT and tryptamine in the presence of iproniazid. 5 The findings in this study suggest that the contractile action of tryptamine in rat caudal artery is mediated predominantly by the same receptor as 5-HT and that the differential inactivation of tryptamine by monoamine oxidase enzymes largely accounts for the different susceptibilities of 5-HT and tryptamine to the antagonists examined.

Animals↗
PubMed1984

Electrophysiological evidence for kappa-agonist activity of dynorphin in rat brain.

Dynorphin (1-13) and the mu-agonist, FK 33,824, have been applied microiontophoretically to single neurones in the hippocampus of the rat. Whereas FK 33,824 predominantly caused an increase in neuronal firing rates, dynorphin (1-13) decreased activity. Both effects were blocked by the opiate antagonist naloxone, whereas the effects induced by GABA and glutamate were not. This action of dynorphin (1-13) is comparable to that of other kappa-agonists in this brain region and suggests that dynorphin (1-13) may be a ligand for the kappa opiate receptor.

Animals↗
PubMed1984

A microiontophoretic study of the actions of mu-, delta- and kappa-opiate receptor agonists in the rat brain.

The actions of mu-, delta- and kappa-opiate receptor agonists have been compared on the activity of single neurones in the brain stem, caudate nucleus and hippocampus of the rat, using the technique of microiontophoresis. In the brain stem and caudate nucleus the predominant effect of all the opiate agonists tested was depression of neuronal activity which was antagonized by naloxone. The selectivity of naloxone as an opiate receptor antagonist was indicated by its lack of effect on gamma-aminobutyric acid (GABA)-induced responses. In the hippocampus both mu- and delta-agonists mainly caused an increase in neuronal firing rates, though some neurones were depressed. In contrast, all the kappa-agonists, including the proposed endogenous ligand for the kappa-receptor, dynorphin, caused depression of neuronal activity. All of these effects were antagonized by naloxone. There was a clear distinction in the areas within the hippocampus in which the mu- and delta-agonists produced different effects. Neurones in the pyramidal cell layer were always excited by these drugs, whereas neurones in the granule cell layer of the dentate gyrus were always depressed by the same drug.

Action Potentials↗
PubMed1983

Cholinoceptive properties of respiratory neurones in the rat medulla.

The effects of iontophoretically applied acetylcholine, the acetylcholine agonists nicotine and muscarine, and the antagonists atropine, dihydro-beta-erythroidine (DH beta E) and mecamylamine, together with the excitatory amino acids, glutamate and D,L-homocysteic acid (DLH) were examined on the activity of respiratory-related neurones in the rat medulla and were compared with effects on non-respiratory brain stem neurones. Most neurones were excited by acetylcholine and no inhibitory responses were seen. Glutamate and DLH also excited but there was a trend for the phasic activity of respiratory neurones to be converted to a tonic discharge. Nicotine also excited most neurones to which it was applied and these responses were blocked by DH beta E but not by atropine. Muscarine also caused excitation and these responses were blocked by atropine but not by DH beta E. Both antagonists blocked acetylcholine-induced excitation but had no effect on responses to glutamate or DLH. Mecamylamine was without effect. It is concluded that the proportion of cholinoceptive respiratory neurones in the rat brain stem is similar to that for non-respiratory neurones. It seems likely that both nicotinic and muscarinic receptors are present on the majority of respiratory neurones and that both contribute to the response produced by iontophoretically-applied acetylcholine.

Acetylcholine↗
PubMed1979

Interactions of (+)-amphetamine and chlorpromazine on neurones in the lower brain stem of the rat.

1 The ability of chlorpromazine to antagonize the effects of iontophoretic application of (+)-amphetamine to single neurones in the medulla and lower pons of anaesthetized rats has been studied. 2 Chlorpromazine, administered systemically or iontophoretically, consistently and specifically antagonized the excitatory actions of (+)-amphetamine, but not those of noradrenaline on the same neurone. 3 It is concluded that chlorpromazine reduces the effect of (+)-amphetamine by a presynaptic mechanism. 4 (+)-Amphetamine did not mimic the prolonged inhibitory response of some neurones to noradrenaline but often excited these neurones and chlorpromazine blocked these excitatory responses to (+)-amphetamine.

Acetylcholine↗