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T D White

Publications and source records attributed to T D White.

At least 91 records · Page 5Linked to original sources
PubMed1987

Involvement of adenosine in the spinal antinociceptive effects of morphine and noradrenaline.

Intrathecal (i.t.) pretreatment of rats with either theophylline (50 micrograms) or 8-phenyltheophylline (3 micrograms) antagonized antinociception produced by i.t. injection of morphine (0.3-3 micrograms) in the tailflick and hotplate tests, but had no effect on antinociception produced by i.t. injection of noradrenaline (10-30 micrograms). In other experiments designed to test whether morphine released adenosine from the spinal cord, adenosine release from synaptosomes was measured by high-performance liquid chromatography with fluorescence detection of etheno-adenosine. Depolarization with 24 mM K+ or 50 microM veratridine released 3 times as much adenosine from dorsal than from ventral spinal cord synaptosomes. K+ released primarily adenosine whereas veratridine released both adenosine and nucleotide(s). Morphine (1-100 microM) produced a Ca++-dependent release of endogenous adenosine, comparable to K+-evoked adenosine release, which was blocked by 1 microM naltrexone. Noradrenaline (5-500 microM) produced a Ca++-dependent release of a nucleotide which was subsequently degraded extracellularly to adenosine by ecto-5'-nucleotidase. This release was antagonized by 10 microM phentolamine and by 1 microM yohimbine. These results suggest that, within the spinal cord, morphine may act on opioid receptors to release adenosine which subsequently acts at adenosine receptors to produce spinal analgesia. Spinal analgesia produced by noradrenaline does not appear to involve adenosine release.

Adenosine↗
PubMed1986

Cut marks on the Bodo cranium: a case of prehistoric defleshing.

Cut marks were discovered on the Middle Pleistocene Bodo cranium from Ethiopia. The cut marks most closely resemble experimental damage caused by the application of stone tools to fresh bone. This discovery constitutes the earliest solid evidence for intentional defleshing of a human ancestor and offers new research avenues for the investigation of early hominid mortuary practices.

Ethiopia↗
PubMed1986

Classification of adenosine receptors mediating antinociception in the rat spinal cord.

Analogues of adenosine were injected intrathecally into rats implanted with chronic indwelling cannulae in order to determine a rank order of potency and hence characterize adenosine receptors involved in spinal antinociception. In the tail flick test L-N6-phenylisopropyl adenosine (L-PIA), cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamide adenosine (NECA) produced dose-related antinociception which attained a plateau level. NECA and CHA also produced an additional distinct second phase of antinociception. D-N6-Phenylisopropyl adenosine (D-PIA) and 2-chloroadenosine (CADO) had very little antinociceptive activity in this test. The rank order of potency in producing the plateau effect was L-PIA greater than CHA greater than NECA greater than D-PIA = CADO, while that for the second phase of antinociception was NECA greater than-CHA. Pretreatment with both theophylline and 8-phenyltheophylline (8-PT) antagonized antinociception produced by CHA, with 8-PT being at least an order of magnitude more potent than theophylline. Both antagonists produced a significant hyperalgesia in the tail flick test. L-PIA and CHA also produced methylxanthine-sensitive antinociception in the hot plate test. These results suggest that activation of A1-receptors in the spinal cord can produce antinociception. Activation of A2-receptors may produce an additional effect, but the relative activity of CHA in this component of activity is unusual.

2-Chloroadenosine↗
PubMed1985

Characteristics of P2 (nucleotide) receptors mediating contraction and relaxation of rat aortic strips: possible physiological relevance.

ATP and ADP relaxed rat aortic strips precontracted with noradrenaline by an endothelium-dependent mechanism. 5'-AMP was much less potent and adenosine was essentially without effect. The metabolically stable analogues alpha,beta-methylene ATP and beta,gamma-methylene ATP further contracted precontracted aorta. Aortic strips, which had not been precontracted with noradrenaline, contracted when exposed to either ATP or alpha,beta-methylene ATP, the latter nucleotide being much more potent than the former. Removal of the endothelium increased the contractions to ATP. ANAPP3 had no effect on the endothelium-dependent relaxations produced by ATP but it antagonized contractions produced by alpha,beta-methylene ATP. These results provide evidence for the possible existence of two subtypes of P2 receptors in rat aorta; a P2 receptor mediating contraction residing on smooth muscle which can be antagonized by ANAPP3 and where alpha,beta-methylene ATP is more potent than ATP, and a P2 receptor mediating relaxation located on the endothelium which cannot be antagonized by ANAPP3 and where ATP is much more potent than alpha,beta-methylene ATP.

Adenosine Diphosphate↗
PubMed1985

Characteristics of K+- and veratridine-induced release of ATP from synaptosomes prepared from dorsal and ventral spinal cord.

K+ and veratridine released 2-3 times more ATP from dorsal than from ventral spinal cord synaptosomes (P2). K+-induced release of ATP was Ca2+-dependent whereas veratridine-induced release was augmented in a Ca2+-free medium. Twenty-one to 24 days after section of the right sciatic nerve of the rat the evoked release of ATP from right dorsal synaptosomes was indistinguishable from release from left dorsal synaptosomes. Although these latter results suggest that ATP may not be a transmitter at primary afferent synapses in the spinal cord, it is possible that sciatic nerve section does not deplete the releasable pool of ATP in primary afferent terminals the releasable pool of ATP in primary afferent terminals or that ATP is also released from interneurons in the dorsal spinal cord.

Adenosine Triphosphate↗
PubMed1985

Nature of extrasynaptosomal accumulation of endogenous adenosine evoked by K+ and veratridine.

When rat brain synaptosomes were incubated for 10 min at 37 degrees C, basal accumulation of adenosine in the medium was 66 pmol/mg of protein. An elevated K+ level (24 mM) evoked an additional accumulation of 200 pmol/mg of protein, and 50 microM veratridine evoked 583 pmol of adenosine accumulation/mg of protein. K+- and veratridine-evoked accumulation of adenosine did not arise from microsomal or mitochondrial contaminants of the synaptosomal preparation, because purified microsomes and mitochondria did not exhibit evoked accumulation of adenosine in the medium. K+-evoked accumulation of extrasynaptosomal adenosine was Ca2+-dependent, whereas veratridine-evoked accumulation of adenosine was increased in Ca2+-free medium. In the presence of alpha,beta-methylene ADP and GMP, which inhibit ecto-5'-nucleotidase, conversion of added ATP and AMP to adenosine was inhibited by 90% in synaptosomal suspensions. However, inhibition of ecto-5'-nucleotidase only reduced basal extrasynaptosomal accumulation of adenosine by 74%, veratridine-evoked accumulation of adenosine by 46%, and K+-evoked accumulation by 33%. Most of the basal accumulation of extrasynaptosomal adenosine appears to be derived from released nucleotide, probably ATP, but about half of the veratridine-evoked accumulation of adenosine and most of the K+-evoked accumulation may arise from adenosine released in its own right, rather than from a released nucleotide.

Adenosine↗
PubMed1985

Adrenergic and possible nonadrenergic sources of adenosine 5'-triphosphate release from nerve varicosities isolated from ileal myenteric plexus.

Pretreatment of guinea pigs with 6-hydroxydopamine in vivo for 24 h (250 mg/kg i.p.) reduced the norepinephrine and tyrosine hydroxylase contents of varicosities isolated from ileal myenteric plexus by 91 and 89%, respectively, indicating extensive destruction of noradrenergic varicosities. Destruction appeared to be restricted to noradrenergic varicosities because 5-hydroxytryptamine contents were unaffected. In vivo 6-hydroxydopamine treatment reduced the K+- and veratridine-evoked release of ATP from myenteric varicosities by 56 and 63%, respectively, indicating that much, but not all, of the evoked release of ATP probably originated from noradrenergic varicosities. Pretreatment of guinea pigs with 5 mg/kg of reserpine i.p. depleted norepinephrine contents of isolated varicosities by 90% but did not significantly reduce K+- or veratridine-evoked release of ATP, suggesting that the exocytotic release process was unaffected by reserpine. Selective destruction of serotonergic varicosities by treatment of guinea pigs with 50 mg/kg of desmethylimipramine i.p. followed by 40 mg/kg of 5,7-dihydroxytryptamine s.c. failed to diminish K+- or veratridine-evoked release of ATP from myenteric varicosities, indicating that the nonadrenergic release of ATP did not arise from serotonergic varicosities.

Adenosine Triphosphate↗
PubMed1985

5-hydroxytryptamine releases adenosine 5'-triphosphate from nerve varicosities isolated from the myenteric plexus of guinea-pig ileum.

5-Hydroxytryptamine (5-HT)-evoked release of ATP from nerve varicosities isolated from the myenteric plexus of guinea pig ileum was investigated. 5-HT released ATP from myenteric varicosities by a Ca2+-dependent mechanism. The EC50 for release of ATP was 7 X 10(-7) M 5-HT. 5-HT-evoked release of ATP was not blocked by tetrodotoxin (TTX), indicating that release was not initiated by the opening of Na+-channels in the isolated myenteric varicosities. Release of ATP by 5-HT was diminished to 56% of control values by in vivo pretreatment of the guinea-pig with 6-hydroxydopamine (6-OHDA, 250 mg kg-1, i.p.) for 24 h. 6-OHDA pretreatment caused extensive destruction of noradrenergic varicosities as indicated by an 87% loss of noradrenaline content. Quipazine (5 X 10(-6) M) and methysergide (10(-4) M) caused a small release of ATP and blocked subsequent 5-HT-induced release of ATP. Metergoline (2.5 X 10(-5) M), (+)-tubocurarine (7 X 10(-5) M) and cocaine (10(-4) M) decreased 5-HT-induced ATP release. 5-Methoxytryptamine (10(-4) M), picrotoxin (3.5 X 10(-6) M), spiroperidol (10(-6) M), morphine (1.3 X 10(-6) M) and phenoxybenzamine (3.7 X 10(-7) M) were ineffective. The results demonstrate a 5-HT-receptor-mediated release of ATP from noradrenergic and possibly non-adrenergic varicosities in the myenteric plexus of guinea-pig ileum. The 5-HT-induced release of ATP is consistent with a possible transmitter, cotransmitter or modulatory role for ATP in the myenteric plexus.

Adenosine Triphosphate↗
PubMed1984

Cranial morphology of Australopithecus afarensis: a comparative study based on a composite reconstruction of the adult skull.

The Pliocene hominid species Australopithecus afarensis is represented by cranial, dental, and mandibular remains from Hadar, Ethiopia, and Laetoli, Tanzania. These fossils provide important information about the cranial anatomy of the earliest known hominids. Because complete crania or skulls are not known, we produced a composite reconstruction of an adult male skull based on 13 specimens from the Hadar Formation. The reconstruction serves as a testable hypothesis regarding functional relationships in the A. afarensis skull and is the basis for the comparative study presented here. We examine six major aspects of cranial and mandibular anatomy. We combine our results with those of White et al. (1981) in a discussion of alternate hypotheses of early hominid phylogeny. In the cranium, jaws, and teeth A. afarensis exhibits a morphological pattern that we interpret as primitive for the Hominidae. Homo habilis retains a number of these primitive features for which A. africanus, A. robustus, and A. boisei share derived character states, particularly in the masticatory apparatus. Homo and "robust" species of Australopithecus share a suite of derived cranial base features. These shared traits may relate to upper facial orthognathium which is also common to these taxa and are probably indicative of parallelism rather than a close phylogenetic relationship. The cranial base characteristics of A.L. 333-45 do not, contrary to Olson's (1981) claims, provide evidence for an A. afarensis--"robust" Australopithecus sister group. When the range of mastoid variation in extant African pongids and A. afarensis is examined thoroughly, the Pliocene hominid appears to retain a primitive, rather than derived, morphology.

Adult↗
PubMed1984

Characteristics of neuronal release of ATP.

Recent studies have described a transmitter-like release of ATP in brain. Once released, extraneuronal ATP is rapidly metabolized to adenosine by ecto-ATPase and nucleotidase. Adenosine, through actions at specific receptors, inhibits neuronal firing in the brain. ATP shares these inhibitory actions, presumably by forming adenosine extraneuronally. Caffeine and theophylline probably exert CNS stimulation by antagonizing adenosine's inhibitory actions in the brain. Extracellular ATP occasionally excites quiescent neurons in the cortex. A possible role for ATP as a sensory neurotransmitter is suggested by its excitatory actions on a subpopulation of dorsal horn cells. ATP release has also been described from sensory nerves in the periphery, motor nerves, nerves of the myenteric plexus, bladder, vas deferens, and from adrenal chromaffin cells and platelets. The possibility that ATP might function as a transmitter, co-transmitter or modulator in the peripheral nervous system is discussed.

Adenosine Triphosphate↗
PubMed1984

Tetrodotoxin-resistant release of ATP from superfused rabbit detrusor muscle during electrical field stimulation in the presence of luciferin-luciferase.

The present study was carried out to assess the possible role of ATP in the noncholinergic, nonadrenergic transmission in the rabbit urinary bladder. When rabbit detrusor muscle strips were superfused with medium containing firefly luciferin-luciferase and stimulated transmurally at low stimulation parameters, tetrodotoxin-sensitive contractions were obtained but no release of ATP could be detected. However, at somewhat higher stimulation parameters, release of ATP was observed. This release of ATP was not diminished by tetrodotoxin indicating that ATP was not likely released as a result of propagated action potentials in nerves. Because contractions persisted in the presence of tetrodotoxin, it is possible that the ATP might have been released as a result of direct electrical stimulation of the muscle. These results do not support the idea that ATP is released as a neurotransmitter in the rabbit bladder.

Adenosine Triphosphate↗
PubMed1983

Acetylcholine releases ATP from varicosities isolated from guinea pig myenteric plexus.

The effects of cholinergic agonists and antagonists on the release of ATP from isolated myenteric varicosities were studied using a firefly luciferin-luciferase technique. In a previous study, acetylcholine and nicotine released ATP from isolated myenteric varicosities, whereas the muscarinic agonist bethanechol did not. In the present study, release of ATP by acetylcholine was shown to be Ca2+ dependent. d-Tubocurarine competitively antagonized the release of ATP by either acetylcholine or nicotine. Maximal release of ATP by acetylcholine (10(-3) M) was approximately 24% that observed with the depolarizing drug veratridine (5 X 10(-5) M), suggesting either that not all of the varicosities capable of releasing ATP possess nicotinic receptors or that acetylcholine does not depolarize the varicosities to the degree that veratridine does. Tetrodotoxin slightly but significantly reduced ATP release induced by acetylcholine or nicotine, indicating some involvement of Na+ channels in the release process. Finally, 6-hydroxydopamine pretreatment produced a 48% reduction in the acetylcholine-evoked release of ATP, suggesting that much, but possibly not all, of the ATP release occurs from noradrenergic varicosities present in the preparation.

Acetylcholine↗
PubMed1982

Lack of effect of 6-hydroxydopamine pretreatment on depolarization-induced release of ATP fron rat brain synaptosomes.

Pretreatment of rats with intraventricular 6-hydroxydopamine produced considerable destruction of noradrenergic and dopaminergic nerve terminals as indicated by depletions in synaptosomal catecholamine contents. However, 6-hydroxydopamine pretreatment did not result in diminished release of ATP during depolarization of synaptosomes with either elevated extracellular K+ or veratridine. These findings suggest that most of the ATP released during the depolarization of rat brain synaptosomal preparations is not co-released with noradrenaline or dopamine but must originate from other sources.

Adenosine Triphosphate↗
PubMed1982

Depolarization-induced release of adenosine 5'-triphosphate from isolated varicosities derived from the myenteric plexus of the guinea pig small intestine.

In order to study the release of ATP from a neuronal preparation thought to be "purinergic," isolated varicosities were prepared from myenteric plexus by mincing and homogenizing the longitudinal muscle of guinea pig ileum in 0.32 M sucrose. The presence of varicosities within the crude preparation (P2), isolated by differential centrifugation, was confirmed by electron microscopy and by the presence of occluded lactate dehydrogenase as a cytoplasmic marker. Varicosities were purified further from the P2 fraction on a discontinuous sucrose density gradient and characterized morphologically. Varicosities resembling cholinergic, "purinergic," and adrenergic axonal terminals were identified. The release of ATP from both crude and purified varicosities was detected by monitoring the light produced when the released ATP reacted with firefly luciferin-luciferase which was present in the incubation medium. Elevated extracellular K+ or Rb+ caused the release of ATP, whereas elevated Na+ and Li+ did not. The release of ATP by either K+ or by the depolarizing drug, veratridine, was Ca2+ dependent. This requirement of extracellular Ca2+ for veratridine-induced release of ATP from isolated myenteric varicosities contrasted strikingly with that for brain synaptosomes, where the release of ATP induced by veratridine was increased rather than decreased in a Ca2+-free medium. The characteristics of ATP release from myenteric varicosities are consistent with a possible neurotransmitter function for ATP in myenteric plexus, although it is also possible that ATP is co-released with some other neurotransmitter.

Adenosine Triphosphate↗
PubMed1979

A systematic assessment of early African hominids.

A large sample of Pliocene fossil hominid remains has been recovered from the African sites of Hadar in Ethiopia and Laetolil in Tanzania. These collections, dating approximately between 2.9 and 3.8 million years ago, constitute the earliest substantial record of the family Hominidae. This article assesses the phylogenetic relationships of the newly discovered fossil hominids and provides a taxonomy consistent with that assessment. A new taxon, Australopithecus afarensis, has been created to accommodate these Pliocene hominid fossils.

Africa, Eastern↗