PubMed Health⌕ Search

Biomedical subjects

A W Fox

Publications and source records attributed to A W Fox.

14 recordsLinked to original sources
PubMed1992

Comparison of peptide and nonpeptide receptor-mediated responses in rat tail artery.

Chronic uremia and metabolic acidosis impair vascular responses to norepinephrine (NE) and also cause multiple metabolic defects in skeletal muscle. These studies were conducted to determine whether decreased vascular responsiveness resulted from putative second messenger metabolism. Tail arteries were used from rats with metabolic acidosis or nonacidotic uremia and from normal controls. In normal arteries, the maximal responses were the same for arginine vasopressin (AVP), NE, and mixtures of the two agonists, suggesting that the two receptor types use the same transduction mechanism. Nonetheless, qualitative differences exist between AVP- and NE-induced responses: (a) Concentration-response curves are steeper for AVP than for NE, (b) EC50 values are similar for AVP between inositol phosphates (IP assays) and contraction, but not for NE, and (c) arteries from rats with metabolic acidosis or uremia show selective blunting of biochemical and contractile responses to NE but not to AVP. We conclude that these metabolic derangements selectively affect alpha-adrenergic receptors, but not AVP receptors or the transduction mechanism leading to contraction.

Acidosis↗
PubMed1991

Informed consent.

Explore the source record for details and available documents.

Ethics, Medical↗
PubMed1989

Speech dysfunction of obstructive sleep apnea. A discriminant analysis of its descriptors.

We have previously demonstrated a relationship between abnormal speech and obstructive sleep apnea in a small subject sample. The present study was designed to replicate the previous one with a much larger population, analyze the perceptual characteristics of the speech quality, and determine the degree to which each of three descriptors of speech abnormality contributed to the perception of speech abnormality. Ten graduate students in speech pathology listened in two 1.5 hour sessions to 252 random speech samples presented on a master tape. There were 81 subjects comprised of 27 sleep apnea patients, 27 matched chronic obstructive pulmonary disease control patients, and 27 matched normal control subjects. Rating the speech along an equally-appearing interval scale from 1 to 7, the judges heard abnormal resonance, articulation or phonation in 74 percent of the sleep apnea subjects, 53 percent of the COPD subjects, and 7 percent of the normal subjects (significant difference by chi 2 test at the .01 level of confidence). Discriminant function equations based on these speech descriptors correctly identified 96.3 percent of the normal subjects and 63.0 percent of the sleep apnea subjects. Analysis of abnormal speech resonance, articulation and phonation may identify obstructive sleep apnea or may provide insight into its pathology.

Adult↗
PubMed1988

Vascular vasopressin receptors.

1. Vascular vasopressin receptors are understood because of the specific application of each major technical advance in pharmacology; this review shows that isolated organs, whole animal preparations, hormone synthesis, radioligand binding, and human studies have all played their part. 2. Even so, neither vascular vasopressin receptor heterogeneity nor occupancy-response relationships are fully understood; by way of comparison far more is known about alpha-adrenoceptors. 3. The biochemical pharmacology of vascular vasopressin receptor activation is still in its infancy. Whilst the second messenger molecules resulting from vascular vasopressin receptor activation appear to be component(s) of the pathways of phosphoinositide metabolism, technical difficulties have led investigators to study similar vasopressin receptors in other tissues. 4. It is not certain, for example, that results from hepatic vasopressin receptor studies can be automatically extrapolated to vascular smooth muscle. 5. Lastly, the directions that vascular vasopressin research might take are speculated on. It is not known whether the vascular vasopressin receptor is itself a polymer, whether receptor heterogeneity could be exploited in the clinical uses of vasopressins, nor whether vasopressins are co-released with other neurotransmitters.

Animals↗
PubMed1987

Vasopressin receptor mediated contraction and [3H]inositol metabolism in rat tail artery.

Inositol phosphates (IP) production and contraction in isolated but otherwise intact rat tail artery were measured in response to stimulation by vasopressin agonists. We have previously studied similar alpha-adrenoceptor responses. Identical rank orders of vasopressin agonists' potency were found for IP accumulation and contraction. The vasopressin analogue [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine,D-arginine8] vasopressin, was shown to be a specific, reversible antagonist for both IP accumulation and contraction by all vasopressin agonists tested. No antagonism of vasopressin induced increases in IP accumulation or contraction were found using phenoxybenzamine. Therefore, in this tissue vasopressin receptors mediate both contraction and IP accumulation; and vasopressin mediated responses appear to be direct effects not mediated via the activation of alpha-adrenoceptors. Demonstration of two entirely different receptors, mediating the same functional response, and which both promote IP production, is consistent with a general obligatory role for phosphoinositide catabolism in receptor mediated vascular smooth muscle contraction.

Animals↗
PubMed1987

Evidence for spare alpha 1-adrenoceptors for the accumulation of inositol phosphates in smooth muscle.

The accumulation of inositol phosphates (IP) in smooth muscle from rat vas deferens and caudal artery was maximally increased 3- to 4-fold in response to exposure of the tissues to 100 microM noradrenaline. Clonidine (up to 3 mM) was a partial agonist. Pretreatment of the tissues with the irreversible alpha-adrenoceptor antagonist phenoxybenzamine (0.3-10 microM) shifted the noradrenaline concentration-response curve to the right before depressing the maximum. The maximum of the clonidine concentration-response curve was depressed without significant change in the EC50 by the same treatment. These data, which are most easily interpreted as demonstrating the presence of a receptor reserve for IP accumulation, are discussed.

Animals↗
PubMed1987

Preliminary observation of speech disorder in obstructive and mixed sleep apnea.

Clinical observation suggested that speech disorder seemed to be associated with sleep apnea. We recorded a standard speech sample from 39 matched subjects in three groups, 13 sleep apnea individuals, 13 subjects with COPD, and 13 subjects without sleep apnea or COPD. Three speech pathologists in a single blind listening task of the recorded samples judged whether or not speech disorder was present. Eight of the sleep apnea subjects were judged to have disordered speech compared to three of the COPD group and one of the non-sleep apnea, non-COPD (normal) group. These results were statistically significant. This supports a clinical impression that speech disorder is more common in sleep apnea than expected. There may be common anatomic and physiologic disturbances present between the two conditions, and perhaps disordered speech is a sign of sleep apnea.

Adult↗
PubMed1987

Noncompetitive blockade of vasopressin-1 receptors in rat tail artery.

To study vasopressin-1 receptor-mediated contraction of the isolated rat tail artery, pseudoirreversible blockade was produced by incubating tissues with 10 nM 1-beta-mercapto,beta,beta,cyclopentamethylene propionic acid, 2(O-me)tyrosine,-8-D-arginine vasopressin and 1.2 mM magnesium. Concentration-response curves to vasopressin agonists were constructed before and during exposure to 1-beta-mercapto,beta,beta,cyclopentamethylene propionic acid, 2(O-me)tyrosine,-8-D-arginine vasopressin, and at three time points after washing out the antagonist. EC50 values (-log M) for arg-vasopressin (AVP, 8.02 +/- 0.16) and arg-vasotocin (AVT, 9.51 +/- 0.12) were unaltered after exposure to the antagonist and washing of the tissues. The control EC50 for lys-vasopressin (LVP, 8.33 +/- 0.09) was significantly lower than after blockade (P less than .05). At each time point after blockade, the intrinsic activity of LVP was greater than either AVP or AVT. Increasing the ambient magnesium ion concentration greater than 1.2 mM did not alter responses to vasopressin agonists. Reducing the ambient magnesium ion from 1.2 mM to zero increased the EC50 values for all vasopressin agonists by 6- to 20-fold, but had no effect on maximal response size, nor on the concentration-response curve for norepinephrine. Pseudoirreversible blockade performed in the absence of magnesium also increased the EC50 for LVP but not for AVP or AVT after exposure to the antagonist. We conclude that LVP has greater efficacy than AVP and AVT at vasopressin receptors in rat tail artery, and that magnesium ions affect only agonist affinity but not efficacy at this vasopressin-1 receptor.

Animals↗
PubMed1985

Activation of alpha 1-adrenoceptors increases [3H]inositol metabolism in rat vas deferens and caudal artery.

Rings of rat vas deferens and caudal artery were incubated with [3H]inositol in Krebs-Ringer bicarbonate buffer containing 10 mM lithium chloride, and the production of water-soluble [3H]inositol phosphates was monitored. Norepinephrine increased [3H]inositol phosphate accumulation 7-fold in rings from vas deferens and 3-fold in rings from caudal artery. Epinephrine, phenylephrine and methoxamine were as effective as norepinephrine, suggesting that these drugs are full agonists in causing this response. Prazosin, phentolamine and yohimbine completely blocked the stimulation by norepinephrine in both tissues with potencies typical of blockade of alpha 1-adrenoceptors. Despite a substantial receptor reserve for alpha 1-adrenoceptor mediated contractile responses, clonidine, p-amino-clonidine, phenylpropanolamine and ephedrine can only cause a partial contractile response in rat vas deferens. However, all of these partial agonists were either as effective or more effective in increasing [3H]inositol phosphate accumulation in rat vas deferens as they were in activating a contractile response. These data suggest that alpha 1-adrenoceptors increase phosphatidylinositol turnover in rat vas deferens and caudal artery, and that there may be a receptor reserve for alpha 1-adrenoceptor mediated increases in [3H]inositol phosphate accumulation in these smooth muscles.

Adrenergic alpha-Agonists↗
PubMed1985

Effects of isoxuprine and nylidrin on adrenoreceptors in rat vas deferens.

The interaction of isoxuprine and nylidrin with alpha 1- and beta 2-adrenoreceptors in rat vas deferens was examined using radioligand binding assays and physiological studies in vitro. Isoxuprine and nylidrin have a greater affinity for binding to alpha 1 (isoxuprine KD = 59 +/- 15 nM; nylidrin KD = 41 +/- 3 nM) than beta 2-(isoxuprine KD = 3,900 +/- 500 nM; nylidrin KD = 900 +/- 50 nM) adrenoreceptors in rat vas deferens. Vas deferens from rats pretreated for 16-24 h with reserpine (3 mg/kg i.p.) were exposed to 10 microM phenoxybenzamine for 15 min to inactivate alpha-adrenoreceptors. Under these conditions high concentrations of both isoxuprine and nylidrin relaxed vas deferens contracted with 55 mM K+, however the relaxation was not blocked by the beta-adrenoreceptor antagonist propranolol (10 microM). Both isoxuprine and nylidrin were potent competitive antagonists of alpha 1-adrenoreceptor mediated contraction of vas deferens. pA2 values for isoxuprine (6.9 +/- .05) and nylidrin (7.1 +/- .08) agreed well with KD values for binding to alpha 1-adrenoreceptors in vas deferens. The greater potency of isoxuprine and nylidrin in inhibiting alpha 1-adrenoreceptors than binding to beta 2-adrenoreceptors or causing nonspecific relaxation suggest that alpha-adrenoreceptor antagonist actions of these drugs may be important in their ability to inhibit smooth muscle tone.

Animals↗
PubMed1985

Thyroid status and adrenergic receptor subtypes in the rat: comparison of receptor density and responsiveness.

The density and functional responsiveness of adrenergic receptor subtypes were determined in tissues from control, hyperthyroid and hypothyroid rats. There was a decrease in sensitivity to isoproterenol in spontaneously beating right atria, electrically driven left atria and field-stimulated vas deferens associated with hypothyroidism, with no change in maximum response. Hyperthyroidism increased the potency of isoproterenol in right atria, but not in left atria or vas deferens. The maximal response to isoproterenol was greatly reduced in hyperthyroid left atria. The potency of procaterol, a partial agonist at beta adrenergic receptors in right atria, was unaltered in hyper- or hypothyroidism, although the maximum stimulation by procaterol was increased in hyperthyroidism. Scatchard analysis of specific [125I]pindolol binding showed that beta adrenergic receptor density was greater in hyperthyroidism than in hypothyroidism in left atria, right atria, ventricles, vas deferens and cerebral cortex, although the proportions of beta-1 and beta-2 adrenergic receptor subtypes did not change. There was no change in the responsiveness of alpha-1 adrenergic receptors mediating contraction of caudal artery and vas deferens or mediating [3H]inositol phosphate accumulation in cerebral cortex in hyperthyroid or hypothyroid rats, although the maximal contraction of caudal artery was significantly reduced in hyperthyroidism. Scatchard analysis of specific [125I]BE 2254 binding showed that alpha-1 adrenergic receptor density was significantly decreased in the ventricles from hyperthyroid rats and increased in the ventricles of hypothyroid rats, but was unchanged in vas deferens, caudal artery and cerebral cortex. Alpha-2 adrenergic receptor density in cerebral cortex, determined by Scatchard analysis of specific [3H] rauwolscine binding, was not altered in hyperthyroid or hypothyroid rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Effect of chronic antacid ingestion on serum gastrin and gastric secretion.

Basal gastrin and acid secretion, and histamine- and food-stimulated acid secretion were examined before and after 6 weeks of regular antacid consumption by 20 normal volunteers, in order to test the hypothesis that regular use of antacids produces gastrin cell hyperplasia, altered gastrin inhibition by acid, and gastric hypersecretion. We found no differences in fasting serum gastrin, basal or maximal histamine-stimulated acid, or acid output in response to a protein meal after consumption of commercial antacids with or without calcium carbonate. The results suggest that normal subjects do not acquire functional hyperactivity of the gastrin mechanism after a period of regular antacid use.

Adult↗