PubMed Health⌕ Search

Biomedical subjects

K G Charlton

Publications and source records attributed to K G Charlton.

13 recordsLinked to original sources
PubMed2000

Antibodies to selected disease agents in translocated wild turkeys in California.

Wild turkeys (Meleagris gallopavo) trapped within California (n = 715) or imported into California from other states (n = 381) from 1986 to 1996 were tested for exposure to certain disease agents. Prevalence of antibody to Mycoplasma gallisepticum, Mycoplasma meleagridis, Salmonella pullorum, Salmonella typhimurium, Newcastle disease virus, and avian influenza virus was low (0-4%) for wild turkeys trapped within California. With the exception of antibody prevalence to M. meleagridis of 33%, the same was true for wild turkeys imported into California from other states. Antibody prevalence to Mycoplasma synoviae was 8-10% for both groups.

Agglutination Tests↗
PubMed1989

Partial agonistic activity of GR43175 at the inhibitory prejunctional 5-HT1-like receptor in rat kidney.

1. The pharmacological effect of the selective 5-HT receptor agonist GR43175 has been studied in the isolated perfused rat kidney with particular reference to the inhibitory prejunctional 5-HT1-like receptor. 2. GR43175 (1 x 10(-8) to 1 x 10(-5) M) inhibited the electrically evoked release of tritium from renal noradrenergic nerves but did not affect the basal (non-stimulated) release of tritium or perfusion pressure. 3. The inhibitory prejunctional action of GR43175, as well as that of 5-HT, was blocked by methiothepin, suggesting that both agonists act at the inhibitory 5-HT1-like site. 4. GR43175, relative to 5-HT, acted as a weak partial agonist at the inhibitory prejunctional 5-HT1-like receptor and antagonized 5-HT-induced inhibition of tritium release, suggesting again that a common site of action is involved. 5. The results support the conclusion that the 5-HT1-like receptor activated by GR43175 in the rat kidney is very similar to that identified in dog saphenous vein and certain other tissues.

Animals↗
PubMed1986

Evidence for a receptor mediated action of norepinephrine distinct from alpha- and beta-adrenoceptors.

The mode of action of (-) norepinephrine (NE) and UK-14,304-18 has been investigated using the cholinergically-evoked 'twitch' response of the electrically stimulated guinea-pig ileum. St 587 and benextramine were employed as antagonists. St 587 acted as a competitive antagonist toward UK-14,304-18, yielding an apparent pA2 value of 7.3. In contrast, St 587 failed to act competitively toward NE. Similarly, benextramine (1 X 10(-5) mol/l) blocked the inhibitory responses to UK-14,304-18 but was considerably less active toward NE. Remaining responses to NE after benextramine were not antagonized by St 587, even at a concentration of 3 X 10(-5) mol/l. It is postulated that NE acts to inhibit the 'twitch' response be evoking two different receptor-mediated events: 1. agonism at the alpha 2-adrenoceptor and 2. agonism at a site which is distinct from the alpha- and beta-subtypes. In the concentrations studied, UK-14,304-18, St 587 and benextramine are postulated to lack affinity for the proposed site. The effect of NE and UK-14,304-18 was also investigated on the contractile responses to exogenously applied histamine. These experiments were done in the presence of muscarinic cholinergic and adrenoceptor blockade. NE inhibited responses to histamine but UK-14,304-18 was inactive. Furthermore, the inhibitory action of NE was stereoselective with the (-) form being 25 times more potent than the (+) enantiomer. These findings suggest the presence of a receptor site for NE which is distinct from cholinergic mechanisms and established alpha and beta-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1986

An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney. Apparent distinction from the 5-HT1A, 5-HT1B and 5-HT1C subtypes.

The present study has identified a receptor for 5-hydroxytryptamine (5-HT) which functions to inhibit the stimulus-induced release of [3H] noradrenaline following sympathetic periarterial nerve stimulation to the isolated perfused rat kidney. In addition to 5-HT (IC30 = 4.5 X 10(-8) mol/l), both 5-carboxamidotryptamine (IC30 = 8 X 10(-9) mol/l) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl) indole (RU-24969, IC30 = 2.5 X 10(-7) mol/l) acted as agonists whereas 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was inactive. The inhibitory effect of 5-HT on the electrically-evoked release of tritium was antagonized in a concentration-dependent manner by methiothepin (IC50 = 4 X 10(-9) mol/l), metergoline (IC50 = 4 X 10(-8) mol/l) and methysergide (IC50 = 1.3 X 10(-7) mol/l) but not by cyproheptadine, ketanserin, mesulergine, (-)-propranolol, (+/-)-pindolol, (+/-)-cyanopindolol, metoclopramide or phentolamine. It is concluded that the receptor to 5-HT conforms to general criteria defining 5-HT1-like receptors but at the present time the receptor site cannot be fitted to the designated 5-HT1A, 5-HT1B or 5-HT1C subtypes.

Animals↗
PubMed1986

Responses to norepinephrine resistant to inhibition by alpha and beta adrenoceptor antagonists.

The mode of action of clonidine and norepinephrine (NE) has been investigated in the isolated transmurally stimulated guinea-pig ileum preparation using rauwolscine, idazoxan and benextramine as antagonists. Both clonidine and NE produced concentration-dependent inhibition of the cholinergically induced twitch response and were antagonized by rauwolscine and idazoxan, but only clonidine was antagonized in a truly competitive fashion. Benextramine, an irreversible alpha adrenoceptor antagonist, in a concentration of 10(-5) M, inhibited the effect of clonidine completely but only partially antagonized the inhibitory action of NE. The antagonism of NE by rauwolscine and benextramine was most pronounced after reserpine pretreatment and blockade of neuronal and extraneuronal uptake. Under these conditions, the concentration-effect curve to NE remaining after treatment with benextramine showed an IC50 of about 3 X 10(-7) M and an intrinsic activity of 0.6. This curve was resistant to further inhibition by clonidine (10(-5) M), phentolamine (3 X 10(-6) M), rauwolscine (3 X 10(-6) M), prazosin (10(-6) M) and propranolol (1.2 X 10(-5) M). Thus, alpha and beta adrenergic receptors do not appear to be involved. It is postulated that NE-induced inhibition of the guinea-pig ileum twitch response is mediated by two distinct sites: one is the classical alpha-2 adrenoceptor (the site of action of clonidine and the alpha adrenoceptor antagonists) whereas the other is a site seemingly unrelated to the alpha and beta subtypes.

Adrenergic alpha-Antagonists↗
PubMed1984

Cardiac norepinephrine releasing action of kynuramine, an endogenous diamine derived from L-tryptophan.

Kynuramine, an endogenous metabolite of L-tryptophan, was found to function as an indirectly acting sympathomimetic amine in rat atria in vitro. Kynuramine released tritium from atria preloaded with [3H]norepinephrine (NE), an effect which was blocked completely by pretreatment with reserpine or 6-hydroxydopamine. Release by kynuramine was calcium-independent and was potentiated by inhibition of monoamine oxidase but was only partially sensitive (50%) to inhibition by cocaine (10(-4)M). The ability of kynuramine to enter cardiac cells was demonstrated in whole atria by measuring its intracellular deamination rate by monoamine oxidase. Blockade of neuronal uptake (cocaine) and extraneuronal uptake (SKF 550) had no effect upon this measure. It is concluded that knyuramine releases cardiac NE, in part, by a cocaine-sensitive mechanism but that the process operating for the membrane transport of kynuramine in both neuronal and non-neuronal cells remains uncertain. The data are discussed in relation to the possible cardiac consequences of L-tryptophan ingestion in man.

Animals↗
PubMed1984

Kynuramine: high affinity for [3H]tryptamine binding sites.

Kynuramine, an endogenously occurring metabolite of L-tryptophan, was found to displace [3H]tryptamine from its high affinity binding sites in rat brain cortex with an inhibition constant (Ki) of 28 nM. Kynuramine exhibited structural specificity and considerable selectivity, compared with its affinity for serotonergic, adrenergic and benzodiazepine recognition sites. This novel finding opens-up the possibility that kynuramine may exert physiological actions via the putative tryptamine receptor.

Animals↗
PubMed1984

Vasoconstrictor and norepinephrine potentiating action of 5-hydroxykynuramine in the isolated perfused rat kidney: involvement of serotonin receptors and alpha 1-adrenoceptors.

Kynuramines are endogenously occurring diamines derived from tryptophan. In the present study, we have compared the pharmacological actions of 5-hydroxykynuramine (5-OH-K) with kynuramine and 5-hydroxytryptamine (5-HT) on vascular resistance changes and responsiveness to adrenergic stimuli in the isolated perfused rat kidney. 5-OH-K was found to mimic the actions of 5-HT in that it produced vasoconstriction, potentiation of alpha 1-adrenoceptor-mediated responses to norepinephrine (NE) and periarterial nerve stimulation, and displaced specific [3H]spiroperidol binding from rat cortical membranes. With regard to all parameters measured, 5-OH-K was about 15-times less active than 5-HT. Vascular responses to 5-OH-K and 5-HT were inhibited noncompetitively by ketanserin and cyproheptadine. Unlike 5-OH-K, kynuramine, failed to evoke vasoconstriction and inhibited vascular responses to NE via alpha 1-adrenoceptors. Thus, kynuramine lacks serotonin receptor agonist activity but possesses alpha 1-adrenoceptor blocking properties. In contrast, 5-OH-K potentiates NE and acts as a serotonin agonist. The present results raise the possibility that kynuramine and 5-OH-K might act as endogenous modulators of serotonergic and adrenergic mechanisms in the renal vascular bed.

Animals↗
PubMed1983

Cardiovascular actions of kynuramine and 5-hydroxykynuramine in pithed rats.

Kynuramines occur endogenously in brain and peripheral tissues as metabolites of indoleamino acids and indolamines but little is known regarding their possible physiological and/or pharmacological activity. The present study has investigated the effects of kynuramine and 5-hydroxykynuramine on the cardiovascular system of pithed rats and attempted to correlate effects seen on adrenergic and serotonergic receptors with ligand binding experiments done in vitro using rat brain membranes. Kynuramine was found to release cardiac catecholamines and to act as a weak partial agonist on vascular alpha-adrenoceptors. Hydroxylation in the 5-position (5-hydroxykynuramine) did not alter cardiac potency but increased pressor activity 100-fold. Vasopressor responses to 5-hydroxykynuramine were mediated via a dual agonistic action on both postsynaptic alpha 2-adrenoceptors and vascular serotonin2 receptors. These findings were supported by ligand binding studies, in which both kynuramine and 5-hydroxykynuramine showed affinity for cortical [3H]spiroperidol and [3H]clonidine binding sites. Overall, the results show that kynuramines can exert peripheral (and possibly central) actions which may prove to be of physiological and/or pharmacological significance.

Adrenergic alpha-Agonists↗
PubMed1983

Pharmacological characterization of alpha-adrenoreceptor subtypes in rat isolated thoracic aorta.

The subtype of alpha-adrenoreceptor mediating contraction in rat isolated thoracic aorta was classified pharmacologically using preferential agonists and antagonists, and by utilizing mixed agonist and antagonist interactions. Noradrenaline was 8 to 10-times more potent at contracting the aorta than phenylephrine and both agonists were about 1000 and 10,000-fold respectively more potent than azepexole (a preferential alpha 2-agonist). Prazosin (a preferential alpha 1-antagonist) inhibited the dose-response curves to noradrenaline and phenylephrine 100 and 1000-times respectively more effectively than either phentolamine or rauwolscine (a preferential alpha 2-antagonist). Furthermore, prazosin (5 x 10(-9) M) completely abolished contractions elicited by a single concentration of azepexole (3 x 10(-4) M). In mixed antagonist studies, rauwolscine (5 x 10(-7) M) failed to shift the dose-response curves to noradrenaline and phenylephrine obtained in the presence of prazosin (5 x 10(-9) M). In mixed agonist experiments, azepexole (3 x 10(-4) M) acted as a partial antagonist toward phenylephrine-induced contractions. The results suggest that the alpha-adrenoreceptor of the rat thoracic aorta is predominantly, if not exclusively, of the alpha 1-subtype.

Animals↗
PubMed1977

Some effects of mazindol, an anorectic drug, on rat brain monoaminergic systems.

Mazindol was devoid of effect both on rat brain steady state levels of 5-HT, 5-HIAA and tryptophan and on the rate of synthesis of 5-HT in the rat brain. Mazindol had no effect on rat brain 5-HT uptake in vivo as determined by the effect of drug pretreatment on the ability of p-chloroamphetamine to lower central 5-HT levels. A large dose of mazindol caused a slight transient decrease in rat brain levels of NA and DA. Blockade of rat brain catecholamine uptake was quantified by studying drug effects on the ability of intraventricularly administered 6-hydroxydopamine to lower brain NA and DA content. Mazindol was an extremely potent inhibitor of rat brain NA uptake in vivo, being 4-5 times more potent than desipramine. Mazindol also blocked rat brain DA uptake. Doses of mazindol needed to release alpha-methyl-m-tyramine from the rat striatum were appreciably greater than the corresponding doses of d-amphetamine. The neurochemical profile of mazindol bears a much closer resemblance to that of d-amphetamine than to that of fenfluramine.

Animals↗