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Biomedical subjects

T C Westfall

Publications and source records attributed to T C Westfall.

At least 91 records · Page 5Linked to original sources
PubMed1982

Inhibition of the electrically induced release of [3H]dopamine by serotonin from superfused rat striatal slices.

The effect of serotonin (5-hydroxytryptamine) on the electrically induced release of [3H]dopamine from superfused slices of the rat striatum has been studied. It was observed that serotonin produced a concentration dependent decrease in the field stimulation-induced release of [3H]dopamine with the threshold concentration being 10(-6) M or lower. Methysergide, in a concentration which did not alter the evoked release, antagonized the inhibitory effect of serotonin. The present results suggest that serotonin should be added to the list of endogenous substances that can influence dopaminergic transmission in the striatum.

Animals↗
PubMed1982

Interaction of naloxone with the opioid receptor complex in vitro.

Previous work from this laboratory suggests that distinct morphine and enkephalin receptors coexist in an opioid receptor complex. In this paper the interaction of naloxone with the receptor complex is studied. The results further strengthens the hypothesis that leucine enkephalin binds poorly to the morphine receptor and that morphine and enkephalin receptors are allosterically coupled.

Animals↗
PubMed1982

Cerebral monoamines and lidocaine toxicity in rats.

The effect of alterations in whole brain monoamine content on the plasma lidocaine concentration resulting in seizures was studied in rats. Reductions in brain monoamine content were produced by treatment with one of the following drugs: reserpine, parachlorophenylalanine (PCPA), or alpha methyl paratyrosine (AMPT). Reserpine depleted norepinephrine (NE), and dopamine (DA) by 75 per cent and serotonin (5HT) by 54 per cent; PCPA reduced brain 5HT 56 per cent without changing NE and DA; AMPT reduced brain NE and DA by 54 and 60 per cent, respectively, without altering 5HT content. Treatment with 5-hydroxytryptophan, a serotonin precursor combined with the peripheral decarboxylase inhibitor RO4-4602 increased brain 5HT content by 400 per cent without changes in DA and NE. Whole brain NE concentrations were assayed fluorometrically, DA brain concentrations were assayed by HPLC, and lidocaine concentrations in plasma were determined by gas chromatography. Plasma lidocaine concentrations at the onset of convulsions were found to be elevated significantly only by drugs causing serotonin depletion; increasing to 128 per cent of control with reserpine treatment and 139 per cent of control with PCPA treatment. Depletion of NE and DA had no effect on the lidocaine seizure threshold. Increases in brain 5HT caused a small but not statistically significant decrease to 94 per cent of control in the mean plasma lidocaine concentration at seizure onset.

Animals↗
PubMed1982

The release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive and Wistar-Kyoto rats.

The potassium (K+)-induced release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive rats has been studied as a function of the development of hypertension. The absolute amount of norepinephrine released by potassium was greater in spontaneously hypertensive rat than the normotensive Wistar-Kyoto rat, regardless of age or blood pressure. However, the %-fractional release was elevated only in the rats with chronic hypertension. Preincubation of tissues with the alpha 2-antagonist, yohimbine, significantly enhanced norepinephrine overflow in all tissues studied. Young hypertensive animals demonstrated an enhancement equal to the Wistar-Kyoto rat controls. In the adult spontaneously hypertensive rat, however, there was a significantly lesser enhancement produced by yohimbine. Levels of norepinephrine in the nerves supplying the artery were greater in the prehypertensive spontaneously hypertensive rat than the age-matched Wistar-Kyoto rat. The norepinephrine content in arteries from adult animals was equivalent. The explanation for the attenuation of the yohimbine effect of chronic hypertensive animals is unclear. Although several explanations are possible, the data are consistent with the hypothesis that spontaneously hypertensive rats with chronic hypertension have subsensitive prejunctional alpha 2-receptors as evidenced by an increased %-fractional release of norepinephrine and a decreased enhancement of overflow in the presence of yohimbine. Clearly, further studies are needed to answer this provocative question and to understand the complex interactions of adrenergic neurotransmission in hypertensive animals.

Animals↗
PubMed1982

Allosteric coupling between morphine and enkephalin receptors in vitro.

In a recent paper from our laboratory [Mol. Pharmacol 21:538-547 (1982)] evidence was presented which suggested that [3H]leucine enkephalin labels a single class of binding sites (the enkephalin receptor) and that morphine allosterically induces a masking of enkephalin receptors as a consequence of binding to a receptor (the morphine receptor) not labeled by the 3H-peptide. Evidence is presented in this paper that [3H]etorphine can be used to label selectively the morphine receptor and that the inhibitory dissociation constants (KI) of morphine, etorphine, and human beta-endorphin for the [3H]etorphine binding site closely approximate the concentration of these drugs which produce a half-maximal decrease in the number of enkephalin receptors. Furthermore, an examination of the interaction of leucine enkephalin and methionine enkephalin with the morphine receptor has demonstrated that the pentapeptides are not competitive inhibitors of [3H] etorphine binding, and that they have much lower affinities for the morphine receptor than previously thought. On the basis of these data, a working hypothesis has been formulated which postulates that distinct morphine and enkephalin receptors coexist in an opioid-receptor complex.

Allosteric Site↗
PubMed1982

Morphine allosterically modulates the binding of [3H]leucine enkephalin to a particulate fraction of rat brain.

Equilibrium binding studies have demonstrated that [3H]leucine enkephalin labels a single class of binding sites in a particulate fraction of rat brain with a dissociation constant (KD) of 3.2 +/- 0.1 nM. Methionine enkephalin was a competitive inhibitor of [3H]leucine enkephalin binding, changing the KD to 14.1 +/- 1.5 nM. In contrast, Scatchard analysis of the binding of [3H]leucine enkephalin in the absence and presence of 10, 50, and 100 nM morphine demonstrated that these concentrations of morphine decreased the number of binding sites by 23%, 32%, and 42%, respectively, with no change in the KD. In contrast, morphine at 500 nM caused a 45% decrease in the number of binding sites and an increase in the KD. On the basis of these data, the inhibitory dissociation constant (KI) of morphine was calculated to 400 +/- 17 nM. The noncompetitive inhibition by morphine of [3H]leucine enkephalin binding was shown to be rapidly reversible, ruling out pseudoirreversible binding of morphine to the enkephalin binding site as the underlying mechanism. Computer analysis of the displacement [3H]leucine enkephalin binding by various concentrations of morphine has demonstrated that an allosteric model, not a two-site model, best describes the observed data. We conclude that at low concentration morphine binds to a receptor not labeled by [3H]leucine enkephalin and by doing so allosterically induces an apparent loss of enkephalin receptors.

Allosteric Site↗
PubMed1981

Allosteric modulation by leucine-enkephalin of [3H]naloxone binding in rat brain.

The interaction of morphine and leucine-enkephalin with the binding site labeled by [3H]naloxone in the presence of sodium was compared. The effect of fixed concentrations of morphine and leucine enkephalin on the saturation binding of [3H]naloxone demonstrated that whereas morphine was a competitive inhibitor, leucine enkephalin caused a dose-dependent masking of binding sites. From these data we conclude that the enkephalin receptor is allosterically coupled to the morphine receptor.

Allosteric Site↗
PubMed1981

Alterations in prejunctional adrenoceptor function in guinea pig and rat vas deferens after chronic ganglionic blockade.

The purpose of the present study was to test the hypothesis that alterations in nerve impulse traffic can influence the activity of substances which act prejunctionally to alter adrenergic neurotransmission. Measurements of the rapid phasic contraction of the isolated rat or guinea-pig vas deferens to short periods of electrical field stimulation were carried out in tissues obtained from saline- or chorisondamine-treated (8 mg/kg twice daily for 5 days) rats and guinea pigs. The alpha-2 selective agonist and antagonist, clonidine, and yohimbine, respectively, were utilized to assess prejunctional alpha-adrenergic function. It was observed that chronic treatment with chlorisondamine in doses that blocked ganglionic transmission produced a subsensitivity of the prejunctional alpha adrenoceptor system as evidenced by the fact that both the alpha-2 agonist, clonidine, and the alpha-2 antagonist, yohimbine, were less effective in decreasing or increasing nerve-stimulated induced contractions of the vas deferens, respectively. The present results are consistent with the idea that interruption of nerve impulse traffic results in a loss or decrease in the function or prejunctional inhibitory systems. Postjunctional supersensitivity of effector cells is an adaptive change in the direction of compensating for a decline in exposure to the neurotransmitter. The physiological success of the adaptation would be further enhanced by an increase in transmitter release consequent to subsensitivity of the presynaptic feedback inhibition.

Animals↗
PubMed1979

Effect of prolactin on dopamine synthesis in medial basal hypothalamus: evidence for a short loop feedback.

Several procedures were utilized to study the effects of prolactin on dopamine synthesis in the medial basal hypothalamus of the rat. Elevation of serum prolactin was produced by the administration of trifluoperazine (5 mg/kg, i.p.) and resulted in a significant increase in the conversion of [3',5'-3H]tyrosine to dopamine when measured in slices of medial basal hypothalamus and striatum. Hypophysectomy abolished this effect of trifluoperazine in the medial basal hypothalamus but not in the striatum. In addition, the synthesis of dopamine was significantly elevated in slices of medial basal hypothalamus obtained from rats bearing pituitary tumor implants that secreted microgram quantities of prolactin. In contrast, the in vitro synthesis of dopamine in the striatum of such rats was increased by the secretory products in one tumor line but decreased in another compared to that observed in control animals. It is suggested that the ability of prolactin to accelerate the synthesis of dopamine in the medial basal hypothalamus might constitute a short loop feedback system that finely regulates prolactin secretion.

Animals↗
PubMed1979

Influence of cholinergic agents on dopamine release from medial basal hypothalamus.

The ability of acetylcholine to influence the stimulation-induced release of [3H]dopamine in medial basal hypothalamus was evaluated. A muscarinic facilitation of electrical field-stimulated but not potassium-stimulated release was observed. These data suggest a muscarinic enhancement of dopamine release perhaps via an action at the level of the cell body. These data suggest that observed effects of cholinergic agents on prolactin release may be mediated in part through such a cholinergic-dopaminergic interaction.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1979

Effect of adenosine on adrenergic neurotransmission in the superfused rat portal vein.

This study examined the effect of exogenously applied adenosine on the release of 3H-norepinephrine from the field-stimulated, superfused rat portal vein. Adenosine was found to inhibit the field-stimulated release of 3H-norepinephrine in a dose-dependent manner in 50- to 1,000-microM concentrations. The effect was reversed when adenosine was washed out. The inhibitory effects of adenosine were antagonized by theophylline (10-4 M) which by itself showed a slight enhancement of stimulated 3H-norepinephrine release. ATP was found to inhibit 3H-norepinephrine release at the same concentration as adenosine while inosine was inactive. When adenosine was tested in the presence of the muscarinic and alpha-adrenergic blocking agents atropine and phenoxybenzamine along with indomethacin, a prostaglandin synthesis inhibitor, its inhibotory effect on the stimulated release of 3H-norepinephrine persisted. It is concluded that adenosine and/or ATP can modulate the nerve-stimulated induced release of norepinephrine presumably by an action on the adrenergic nerve terminals.

Adenosine↗
PubMed1978

Effects of adrenalectomy and adrenal steroids on norepinephrine synthesis and monamine oxidase activity.

Rat heart norepinephrine (NE) tunover was increased 6--10 days after bilateral adrenalectomy. This increase was prevented by administration of deoxycorticosterone acetate (DOCA) but not by either hydrocortisone or corticosterone. Blood pressure decreased following adrenalectomy. This decrease was prevented by DOCA, hydrocortisone and corticosterone. Monoamine oxidase (MAO) activity increased in the heart but not in the liver following adrenalectomy. DOCA prevented the increase in heart MAO activity whereas hydrocortisone and corticosterone were ineffective. In intact animals, heart and liver MAO activity were not changed by 5 days of cold exposure, a procedure which increases NE turnover. It is suggested that the increase in heart NE turnover may be related to the increase in MAO activity seen after adrenalectomy.

Adrenal Cortex Hormones↗