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T D White

Publications and source records attributed to T D White.

At least 73 records · Page 4Linked to original sources
PubMed1990

N-methyl-D-aspartate, kainate and quisqualate release endogenous adenosine from rat cortical slices.

N-Methyl-D-aspartate, kainate, and quisqualate released endogenous adenosine from superfused slices of rat parietal cortex. N-Methyl-D-aspartate-evoked adenosine release was blocked by D,L-2-amino-5-phosphono-valeric acid and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), indicating that it was receptor-mediated, although it did not show the expected potentiation in the absence of Mg2+. In contrast, N-methyl-D-aspartate-evoked release of [3H]noradrenaline from the same slices was markedly potentiated in Mg2(+)-free medium. Therefore, the lack of Mg2+ modulation of N-methyl-D-aspartate-evoked adenosine release was not due to depolarization-induced alleviation of the Mg2+ block in the slices. Kainate-evoked adenosine release was diminished by the non-specific excitatory amino acid antagonist, gamma-D-glutamyl-glycine, and kainate- and quisqualate-evoked adenosine release was diminished by 6,7-dinitroquinoxaline-2,3-dione, indicating that these agonists release adenosine by acting at non-N-methyl-D-aspartate receptors. Tetrodotoxin decreased N-methyl-D-aspartate- and kainate-evoked adenosine release by 40% and 19% respectively, indicating that release was mediated in part by propagated action potentials in the slices. Total release of adenosine by N-methyl-D-aspartate, kainate or quisqualate was not diminished in the absence of Ca2+. A second exposure to kainate following restoration of Ca2+ to slices previously depolarized in the absence of Ca2+ resulted in an amount of adenosine release equal to an initial release by slices in the presence of Ca2+, a result suggesting the presence of separate Ca2(+)-dependent and Ca2(+)-independent pools of adenosine. The present experiments demonstrate that activation of all three major subtypes of excitatory amino acid receptors in the cortex releases adenosine, possibly from separate Ca2(+)-dependent and -independent pools. Adenosine released from the cortex following excitatory amino acid stimulation may, by acting at inhibitory P1 purinoceptors, diminish excitatory neurotransmission and protect against excitotoxicity.

2-Amino-5-phosphonovalerate↗
PubMed1990

Glutamate-evoked release of endogenous adenosine from rat cortical synaptosomes is mediated by glutamate uptake and not by receptors.

L-Glutamate (10 microM-1 mM) released endogenous adenosine from rat cortical synaptosomes. Studies with excitatory amino acid antagonists, (+)-5-methyl-16,11,dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), 6,7-dinitroquinoxaline-2,3-dione (DNQX), Mg2+, and agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate, indicated that this release was not receptor mediated. D,L-2-Amino-4-phosphonobutanoic acid (APB) also did not affect glutamate-evoked adenosine release. Inhibition of glutamate uptake by dihydrokainate or replacement of extracellular Na+ blocked glutamate-evoked adenosine release. D-aspartate, which is a substrate for the glutamate transporter but is not metabolized, also released adenosine, suggesting that release was due to amino acid transport and not to its subsequent metabolism. D-Glutamate, a relatively poor substrate for the transporter, was correspondingly less potent than L-glutamate at releasing adenosine. Glutamate-evoked adenosine release was not Ca2+ dependent or tetrodotoxin sensitive and did not appear to occur on the bidirectional nucleoside transporter. Inhibition of ecto-5'-nucleotidase virtually abolished glutamate-evoked adenosine release, indicating that adenosine was derived from extracellular metabolism of released nucleotide(s). However, L-glutamate did not release ATP and did not appear to release cyclic AMP. Therefore, transport of glutamate into presynaptic terminals releases some other nucleotide which is converted extracellularly to adenosine. This adenosine could act at P1-purinoceptors to modulate glutamatergic neurotransmission.

Adenosine↗
PubMed1990

Role of excitatory amino acid receptors in K+- and glutamate-evoked release of endogenous adenosine from rat cortical slices.

K+ and glutamate released endogenous adenosine from superfused slices of rat parietal cortex. The absence of Ca2+ markedly diminished K+- but not glutamate-evoked adenosine release. Tetrodotoxin decreased K+- and glutamate-evoked adenosine release by 40 and 20%, respectively, indicating that release was mediated in part by propagated action potentials in the slices. Inhibition of ecto-5'-nucleotidase by alpha,beta-methylene ADP and GMP decreased basal release of adenosine by 40%, indicating that part of the adenosine was derived from the extracellular metabolism of released nucleotide. In contrast, inhibition of ecto-5'-nucleotidase did not affect release evoked by K+ or glutamate, suggesting that adenosine was released as such. Inhibition of glutamate uptake by dihydrokainate potentiated glutamate-evoked release of adenosine. Glutamate-evoked adenosine release was diminished 50 and 55% by the N-methyl-D-aspartate (NMDA) receptor antagonists, DL-2-amino-5-phosphonovaleric acid and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), respectively. The remaining release in the presence of MK-801 was diminished a further 66% by the non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, suggesting that both NMDA and non-NMDA receptors were involved in glutamate-evoked adenosine release. Surprisingly, K+-evoked adenosine release was also diminished about 30% by NMDA antagonists, suggesting that K+-evoked adenosine release may be partly mediated indirectly through the release of an excitatory amino acid acting at NMDA receptors.

Adenosine↗
PubMed1990

Neural release of ATP and adenosine.

Release of ATP can be evoked from noradrenergic nerve varicosities isolated from guinea pig ileal myenteric plexus by depolarization with K+ and veratridine and during exposure to acetylcholine or 5-HT. Clonidine, however, modulates the release of [3H]noradrenaline without affecting the release of ATP. ATP is also released from noradrenergic sympathetic nerves in the vas deferens, where it mediates the initial depolarization and contraction in the smooth muscle. Factors that apparently modulate the release of noradrenaline do not produce corresponding effects on ATP release. The above results are best explained by the hypothesis that ATP and noradrenaline are stored in separate populations of vesicles within sympathetic nerves and that these pools are subject to differential presynaptic modulation. Depolarization of rat brain synaptosomes releases adenosine by a process that is mediated, at least in part, by efflux on the nucleoside transporter. Drugs that block the nucleoside transport (such as dipyridamole) reduce evoked adenosine release and may thereby diminish, rather than augment, the actions of adenosine at its receptors. Release of adenosine does not appear to be uniformly distributed throughout the brain insofar as release varies from synaptosomes prepared from different regions. Although the distribution of several markers for possible adenosine pathways in the brain, including adenosine release, do not show any consistent correlations, the non-uniform distribution for these markers suggests that adenosine may have differential functions in various brain regions.

Adenosine↗
PubMed1990

A comparison of N-methyl-D-aspartate-evoked release of adenosine and [3H]norepinephrine from rat cortical slices.

Tetrodotoxin reduced N-methyl-D-aspartate (NMDA)-evoked release of adenosine by 35% but virtually abolished [3H]norepinephrine release. Although [3H]norepinephrine release from rat cortical slices evoked by 500 microM NMDA was abolished by 1.2 mM Mg++, which produces a voltage-sensitive, uncompetitive block of NMDA-channels, adenosine release was increased in the presence of Mg++. Partial depolarization with 12 mM K+ relieved the Mg++ block of 500 microM NMDA-evoked [3H]norepinephrine release but did not affect adenosine release, indicating that a Mg++ requirement for the adenosine release process per se cannot account for this discrepancy. NMDA was 33 times more potent in releasing adenosine than [3H]norepinephrine. At submaximal concentrations of NMDA (10 and 20 microM), adenosine release was augmented in Mg+(+)-free medium. Although a high concentration of the uncompetitive NMDA antagonist MK-801 [(+)-5-methyl-10,11,dihydro-5H-dibenzo[a,d]cyclohepten-5-10-imine maleate] (3 microM) blocked NMDA-evoked release of [3H]norepinephrine and adenosine, a lower concentration (300 nM) decreased NMDA-evoked [3H]norepinephrine release by 66% without affecting adenosine release. These findings suggest that maximal adenosine release occurs when relatively few NMDA receptors are activated, raising the possibility that spare receptors exist for NMDA-evoked adenosine release. Rather than acting as a protectant against excessive NMDA excitation, released adenosine might provide an inhibitory threshold which must be overcome for NMDA-mediated neurotransmission to proceed.

Adenosine↗
PubMed1989

An analysis of epipubic bone function in mammals using scaling theory.

Linear dimensions of epipubic bones in 61 species of metatherians and monotremes scale to mass differently in groups with or without marsupia, presumably reflecting emphasis on different but non-mutually exclusive functions. Sexual dimorphism of epipubic form exists. However, the allometric relationships of the epipubic bones of taxa that possess marsupia do not conform to the hypothesis that epipubic bones support the marsupium nearly as well as those without a marsupium. This observation renders a new hypothesis relating litter mass to epipubic form in taxa without marsupia. It appears that support of the marsupium is not the primary function or, at least, not the most proximate determinate of epipubic form in taxa with marsupia. The scaling of epipubic bone dimensions is consistent with the hypothesis that predicts epipubic bones serve to assist in locomotion by acting with the hypaxial muscles of the trunk and pectineus to protract the pelvic limbs. Epipubic length is shown to scale to maintain a mechanical advantage between these opposing muscle groups that approximates the rate that inertia of the hind limbs increases with total mass and speed of locomotion. This hypothesis provides an explanation for a skeletal element scaling significantly above geometric similarity. This observation has important theoretical significance as it suggests that skeletal architecture may, within limits, scale independently of mass-related stress.

Animals↗
PubMed1989

Evoked release of endogenous adenosine from rat cortical slices by K+ and glutamate.

Release of endogenous adenosine from rat cortical slices was determined in response to depolarization by 30 mM K+ and by exposure to glutamate. K+ and glutamate both released adenosine. Glutamate-evoked release was decreased by approximately 50% in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid (APV). The adenosine released by glutamate could modulate neurotransmission, and may have a protective effect in pathologic conditions of excess excitation involving glutamate.

2-Amino-5-phosphonovalerate↗
PubMed1989

Engis: preparation damage, not ancient cutmarks.

Scratches found on the Engis 2 cranium have been described as perimortem and interpreted as intentional scalping marks by Russell and LeMort (Am. J. Phys. Anthropol. 69:317-323, 1986). These marks are described and compared to damage on other fossil hominids. The Engis marks have been misinterpreted. These marks are sandpaper striae formed during restoration of the vault, moulding striae formed when mold part lines were incised into the fossil and profiling striae formed when craniograms were made with sharp steel instrument tips. None of them have anything to do with prehistoric behavior.

Animals↗
PubMed1989

Adenosine release may mediate spinal analgesia by morphine.

Spinal analgesia produced by morphine is blocked by methylxanthine adenosine receptor antagonists. In biochemical studies, morphine releases adenosine from spinal cord synaptosomes prepared from the dorsal spinal cord, as well as from the intact spinal cord in vivo. Adenosine release is reduced by intrathecal and neonatal pretreatment with capsaicin but not by intrathecal pretreatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine, indicating that adenosine originates from small-diameter primary afferent neurons but not descending monoaminergic pathways. In this Viewpoint Jana Sawynok and colleagues review the evidence supporting the hypothesis that the spinal analgesic action of morphine is due to the release of adenosine from primary afferent nerve terminals and subsequent activation of A1 and A2 adenosine receptors.

Adenosine↗
PubMed1989

Morphine, capsaicin and K+ release purines from capsaicin-sensitive primary afferent nerve terminals in the spinal cord.

In the present study the neuronal source of adenosine released by K+, morphine and norepinephrine (NE) from the spinal cord was investigated. Intrathecal pretreatment with 5,7-dihydroxytryptamine and 6-hydroxydopamine reduced spinal 5-hydroxytryptamine and NE levels, respectively, but had no effect on adenosine release from dorsal spinal cord synaptosomes evoked by K+ or morphine. NE-evoked release of adenosine was unaffected by 5,7-dihydroxytryptamine but increased by 6-hydroxydopamine. Subcutaneous pretreatment of neonatal or intrathecal pretreatment of adult rats with capsaicin increased nociceptive thresholds and reduced the release of adenosine evoked by K+ and morphine but not NE from dorsal spinal cord synaptosomes. Intrathecal capsaicin also inhibited morphine-evoked release of adenosine in vivo. K+ and morphine released only small amounts of adenosine from ventral spinal cord synaptosomes whereas NE released significant amounts. Exposure of dorsal, but not ventral, spinal cord synaptosomes to capsaicin produced a dose- and Ca++-dependent release of adenosine, which was reduced by capsaicin pretreatment (neonatal and adult) and inhibition of ecto-5'-nucleotidase. Capsaicin also released endogenous ATP from dorsal spinal cord synaptosomes. These results suggest that primary afferent nerve terminals in the dorsal horn of the spinal cord release adenosine in response to morphine and K+, and a nucleotide (possibly ATP) in response to capsaicin. Adenosine does not appear to be released from the terminals of descending aminergic pathways. The source of purines released by NE is less certain.

Adenosine↗
PubMed1988

Role of adenine compounds in autonomic neurotransmission.

Clearly adenine compounds exert numerous effects throughout the autonomic nervous system. The responses of various peripheral tissues to purines are summarized in Table 2. The evidence supporting a possible excitatory neurotransmitter function for ATP is very good in the vas deferens and good in both the bladder detrusor and certain blood vessels. ATP may also be an excitatory neurotransmitter in the colon, hepatocytes and frog atrium. These responses appear to be mediated by P2x-purinoceptors. There is good evidence supporting a role for ATP as an inhibitory neurotransmitter in the taenia coli and duodenum, and some support in the anal sphincter and possibly the rabbit portal vein; these responses appear to be mediated by P2y-purinoceptors. There is good evidence against ATP being an inhibitory neurotransmitter in the stomach fundic muscle and ileum. ATP (or more likely its metabolite adenosine) may act as an inhibitory neurotransmitter by interacting with postsynaptic P1-purinoceptors in cultured sympathetic neurones and also in the parasympathetic vesicle ganglion of the cat. It seems likely that ATP released from heart, platelets or vascular endothelium could be an endogenous relaxant of blood vessels through its actions on the endothelium. Although the addition of exogenous adenosine affects many tissues, evidence supporting modulatory functions for endogenous extracellular adenosine has only been clearly demonstrated in the ileum, gallbladder, vas deferens, fallopian tubes, kidney, blood vessels, carotid sinus, heart and adipose tissue. Both ATP and adenosine, released during periods of hypoxia or ischemia, could exert negative inotropic, chronotropic and dromotropic actions in the heart. In many cases, the potential sources of extracellular purines have not been established. This is particularly important when attempting to establish a neurotransmitter function for ATP in a tissue. For instance, the one outstanding piece of evidence required to confirm that ATP is an excitatory neurotransmitter released from sympathetic nerves in blood vessels is the unequivocal demonstration that it is, in fact, released from the sympathetic nerves when they are stimulated. To date, only the release of radiolabeled metabolites of ATP, possibly from post- rather than presynaptic sites, has been detected. Studies of the release of ATP are complicated by its rapid degradation extracellularly by ecto-ATPase. Unfortunately, there are no specific inhibitors of ecto-ATPase available at present, but one hopes that a suitable inhibitor will be developed shortly.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗
PubMed1988

Evoked secretion of [3H]noradrenaline and ATP from nerve varicosities isolated from the myenteric plexus of the guinea pig ileum.

Neuronal varicosities, isolated from the myenteric plexus of guinea pig ileum longitudinal muscle, were incubated with [3H]noradrenaline to label the contents of the noradrenergic secretory vesicles. Exposure of these varicosities to KCl, nicotine, or acetylcholine resulted in the Ca2+ -dependent release of [3H]noradrenaline. Veratridine also evoked a large efflux of [3H] from this preparation, but this release was only partially Ca2+ dependent. The alpha 2-adrenoceptor agonist, clonidine, inhibited the K+-, nicotine-, and acetylcholine-induced release of [3H]noradrenaline. Similarly, exogenously administered (-)noradrenaline was an effective inhibitor of the K+ -evoked release of [3H]noradrenaline. The alpha 2-adrenoceptor antagonist, yohimbine, antagonized the inhibitory actions of both clonidine and (-)noradrenaline on the K+ -evoked release of [3H]noradrenaline from myenteric varicosities. Nicotine, acetylcholine, KCl, and veratridine also released ATP from these guinea pig ileal myenteric varicosities. However, the evoked release of ATP was unaffected by clonidine. These results indicate that myenteric varicosities can take up and release [3H]noradrenaline and that they possess presynaptic alpha 2-adrenoceptors which, when activated, inhibit the release of [3H]noradrenaline. These receptors may play a role in modulating the release of noradrenaline in the myenteric plexus in vivo. In addition, the present results suggest that ATP and [3H]noradrenaline may not be released from the same population of secretory vesicles in neuronal varicosities isolated from guinea pig ileum longitudinal muscle.

Acetylcholine↗
PubMed1987

Relaxant effects of ATP and adenosine on canine large and small coronary arteries in vitro.

Rings from greyhound large (3-4 mm internal diameter) and small (less than 200 microns internal diameter) coronary arteries were mounted in water-jacketed tissue baths or a Mulvany myograph, respectively. Relaxations to ATP and adenosine were determined in arteries precontracted with the thromboxane A2 mimetic U46619 or with K+. ATP was a much more effective relaxant of large arteries than adenosine. ATP relaxed large coronaries by an endothelium-dependent mechanism whereas relaxations to adenosine were not endothelium-dependent. In contrast, adenosine appeared to be slightly more effective than ATP in relaxing small coronary arteries. Moreover, adenosine was more effective in relaxing K+-contracted small coronaries than K+-contracted large coronary arteries. These results suggest that ATP may be a more significant relaxant of large coronaries than adenosine but that adenosine may be a more significant relaxant than ATP in small coronary arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Hominid footprints at Laetoli: facts and interpretations.

The history of discovery and interpretation of primate footprints at the site of Laetoli in northern Tanzania is reviewed. An analysis of the geological context of these tracks is provided. The hominid tracks in Tuff 7 at Site G in the Garusi River Valley demonstrate bipedality at a mid-Pliocene datum. Comparison of these tracks and the Hadar hominid foot fossils by Tuttle has led him to conclude that Australopithecus afarensis did not make the Tanzanian prints and that a more derived form of hominid is therefore indicated at Laetoli. An alternative interpretation has been offered by Stern and Susman who posit a conforming "transitional morphology" in both the Tanzanian prints and the Ethiopian bones. The present examines both hypotheses and shows that neither is likely to be entirely correct. To illustrate this point, a reconstruction of the foot skeleton of a female A. afarensis is undertaken, and the results are compared to the Laetoli tracks. We conclude that A. afarensis represents the best candidate for the maker of the Laetoli hominid trails.

Dermatoglyphics↗
PubMed1987

Direct and continuous detection of ATP secretion from primary monolayer cultures of bovine adrenal chromaffin cells.

A method was developed for direct and continuous detection of secretion of ATP from primary monolayer cultures of bovine adrenal chromaffin cells. ATP, which is costored with catecholamines within adrenal chromaffin cells, was released into the incubation medium, where it reacted with firefly luciferin-luciferase producing light detected by a photomultiplier located directly below the culture well. Acetylcholine, nicotine, the Ca2+ ionophore A23187, BaCl2, and KCl induced release of ATP. Induction of release of ATP by acetylcholine was dose dependent, with a threshold at 10(-7) M and a maximum at 10(-4) M. The dose-response curve for nicotine was bell shaped, with a threshold at 10(-7) M, a maximum at 10(-5) M, and diminished release at higher concentrations, an observation indicative of desensitization. Investigation of the initial rates of ATP secretion revealed that 10(-4) M nicotine actually induced release of ATP at a faster rate than 10(-5) M nicotine. However, the rate of ATP release evoked by 10(-4) M nicotine began to decline by 6 s, a result indicating the onset of receptor desensitization, whereas release induced by 10(-5) M nicotine continued unabated. Induction of release of ATP by acetylcholine or nicotine was biphasic, with a rapid, initial phase of release followed by a plateau at 0.5-1.5 min and a second phase of release beginning at 1.5-2 min, reaching a maximum by 2-3 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Release of endogenous ATP during sympathetic nerve stimulation.

1 Vas deferens from guinea-pig was stimulated with a suction electrode and both contractions and release of endogenous ATP monitored 2 Release of ATP was tetrodotoxin-sensitive and increased when the number of stimuli was increased. 3 Release of ATP was not due to contraction of the muscle and persisted following block of contractions with prazosin and alpha, beta-methylene ATP. 4 These results indicate that stimulation of the sympathetic nerves in the vas deferens releases endogenous ATP presynaptically, supporting a cotransmitter function for ATP with noradrenaline.

4-Aminopyridine↗