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C A Briggs

Publications and source records attributed to C A Briggs.

51 records · Page 3Linked to original sources
PubMed1988

Long-term regulation of synaptic acetylcholine release and nicotinic transmission: the role of cyclic AMP.

1. Using the rat superior cervical ganglion in vitro, the relative efficacy of nicotinic synaptic transmission was estimated by recording the postganglionic compound action potential and the amount of endogenous acetylcholine (ACh) released. These two parameters were correlated in individual ganglia by sampling the bathing medium for the assay of ACh while simultaneously recording the postganglionic response. 2. The beta-adrenoceptor agonist isoprenaline potentiated both the evoked release of ACh and the postganglionic response by about 20% during preganglionic stimulation at 0.2 Hz. 3. The adenosine receptor agonist 2-chloroadenosine inhibited ACh release and the postganglionic response by about 35%. 4. Tetanic preganglionic stimulation for a few seconds induced a long-term potentiation of nicotinic responses and of ACh release. Both of these potentiations were dependent upon extracellular Ca2+ during the tetani. 5. Forskolin and analogues of cyclic AMP also caused a long-lasting potentiation of both the evoked release of ACh and the postganglionic response, indicating that cyclic AMP may regulate transmission by a presynaptic mechanism. The specificity of the cyclic AMP analogues was tested using various butyryl- and bromo-purine nucleotides. 6. The effects of forskolin and 8-bromo-cyclic AMP did not appear to be dependent upon extracellular Ca2+. 7. The potentiation caused by forskolin was consistently augmented by three phosphodiesterase inhibitors--AH 21-132, papaverine and SQ 20-006. However, the effect of forskolin was not consistently enhanced by theophylline, nor was it reduced by the adenylate cyclase inhibitor SQ 22-536. 8. The neurogenic long-term potentiation was augmented by two of the phosphodiesterase inhibitors that also augmented the forskolin-induced potentiation--papaverine and SQ 20-006. 9. It was concluded that cyclic AMP can enhance nicotinic transmission, and can do so by increasing the evoked release of ACh. However, it was not possible to prove that cyclic AMP mediates the long-term potentiation induced by tetanic preganglionic stimulation.

Acetylcholine↗
PubMed1988

Long-term potentiation at nicotinic synapses in the rat superior cervical ganglion.

1. Nicotinic fast excitatory postsynaptic potentials (fast EPSPs) were recorded intracellularly from postganglionic neurones in the isolated rat superior cervical ganglion. 2. An hours-long potentiation of the fast EPSP could be induced by brief tetanic stimulation of the preganglionic nerve (5 Hz for 5 s to 20 Hz for 20 s). While long-term potentiation (LTP) can be detected in every ganglion by extracellular techniques, LTP was induced in only two-thirds of the nicotinic synaptic responses. 3. Muscarinic blockade with atropine did not prevent LTP of the fast EPSP. 4. LTP of the fast EPSP did not correlate with changes in input resistance nor cell potential, as recorded in the soma. 5. The formation of nicotinic LTP appeared to depend upon stimulation of the nerve terminals. Non-synaptic tetanic depolarization of the postganglionic neurone, effected by injecting depolarizing current pulses through the intracellular microelectrode, was not sufficient. LTP could be induced by synaptic tetani in two-thirds of the same neurones. 6. The response to exogenous 1,1-dimethyl-4-phenylpiperazinium (DMPP), a selective nicotinic agonist, was not increased during nicotinic synaptic LTP. This was true whether DMPP was applied by pressure-ejection from an extracellular micropipette during intracellular recording, or by brief superfusion during sucrose-gap recording of postganglionic responses. 7. Responses to exogenous acetylcholine and carbachol were increased during nicotinic LTP when these non-selective cholinergic agonists were applied by pressure-ejection during intracellular recording. However, the potentiation of the fast EPSP was always at least twofold greater than the potentiation of the response to these exogenous agonists. 8. Potentiation of the responses to acetylcholine and carbachol may have been due to long-term enhancement of muscarinic responses. Thus, no postsynaptic basis for nicotinic LTP was uncovered in these studies.

Acetylcholine↗
PubMed1988

Effect of carbohydrate ingestion on exercise metabolism.

Five male cyclists were studied during 2 h of cycle ergometer exercise (70% VO2 max) on two occasions to examine the effect of carbohydrate ingestion on muscle glycogen utilization. In the experimental trial (CHO) subjects ingested 250 ml of a glucose polymer solution containing 30 g of carbohydrate at 0, 30, 60, and 90 min of exercise; in the control trial (CON) they received an equal volume of a sweet placebo. No differences between trials were seen in O2 uptake or heart rate during exercise. Venous blood glucose was similar before exercise in both trials, but, on average, was higher during exercise in CHO [5.2 +/- 0.2 (SE) mmol/l] compared with CON (4.8 +/- 0.1, P less than 0.05). Plasma insulin levels were similar in both trials. Muscle glycogen levels were also similar in CHO and CON both before and after exercise; accordingly, there was no difference between trials in the amount of glycogen used during the 2 h of exercise (CHO = 62.8 +/- 10.1 mmol/kg wet wt, CON = 56.9 +/- 10.1). The results of this study indicate that carbohydrate ingestion does not influence the utilization of muscle glycogen during prolonged strenuous exercise.

Adult↗
PubMed1988

Role of cartilage canals in osteogenesis and growth of the vertebral centra.

Bone formation in the vertebral centra commences within the centrum and is in this respect analogous to the secondary ossification which occurs in the epiphysis of a long bone. Bone tissue first appears at about the 85 mm C.R. stage and not in the 55 mm C.R. length embryo; at the latter stage blood vessels and calcification alone were observed. The connective tissue cells within the cartilage canal appear to assist osteogenesis by providing osteogenic cells which lay down bone in the walls of the cartilage canal, and provide cells which remove calcified cartilage found at the periphery of the canal; they assist growth by producing an appreciable number of chondrocytes that permit lateral expansion of the centra. Osteogenesis appears to occur in multiple foci within the growth plate of the older embryos and could account for the rapid rate of growth of vertebrae. Bone formation occurs in both mineralised and unmineralised matrix (as seen on the walls of the cartilage canals). The blood vessels within the growing vertebra tend to follow the zone of cartilage hypertrophy.

Cartilage↗
PubMed1985

Lateral epicondylitis. A review of structures associated with tennis elbow.

139 limbs from embalmed specimens were dissected to reveal the attachments of extensor muscles in the vicinity of the lateral epicondyle. M. extensor carpi radialis brevis was found to consist of a keel-shaped tendon with attachments to m. extensor carpi radialis longus, m. extensor digitorum communis, m. supinator; and to the radial collateral ligament, the orbicular ligament, the capsule of the elbow joint and the deep fascia. On 29 limbs, a prolongation of the muscle was identified attaching proximal to the lateral epicondyle. On nine specimens a bursa was evident between the capsule over the head of the radius and the overlying soft tissues. There was no evidence of variation in vascular or nerve supply to the region. Examination of m. extensor carpi radialis brevis while under tension across the elbow, forearm and wrist revealed the greatest muscle lengthening in pronation of the forearm with palmar flexion and ulnar deviation. The results of this study support the hypothesis that tennis elbow is primarily a mechanically-induced condition. When performing movements at the wrist, with the forearm in pronation, the muscle is at its maximum length. As its origin lies proximal to the axis of rotation for flexion and extension at the elbow, it is subject to shearing stress in all movements of the forearm, especially those involving power at the wrist. This is further compounded by the head of the radius rotating anteriorly against m. extensor carpi radialis brevis during pronation of the forearm. Additionally, a number of individuals may experience pain at the head of the radius during pronation, due to irritation of an underlying bursa.

Elbow↗
PubMed1985

Effects of neuronal activity on inositol phospholipid metabolism in the rat autonomic nervous system.

The effect of nerve stimulation on inositol phospholipid hydrolysis in autonomic tissue was assessed by direct measurement of [3H]inositol phosphate production in ganglia that had been preincubated with [3H]inositol. Within minutes, stimulation of the preganglionic nerve increased the [3H]inositol phosphate content of the superior cervical sympathetic ganglion indicating increased hydrolysis of inositol phospholipids. This effect was blocked in a low Ca2+, high Mg2+ medium. It was also greatly reduced when nicotinic and muscarinic antagonists were present together in normal medium. However, neither the nicotinic antagonist nor the muscarinic antagonist alone appeared to be as effective as both in combination. In other experiments, stimulation of the vagus nerve caused dramatic increases in [3H]inositol phosphate in the nodose ganglion but did not increase [3H]inositol phosphate in the nerve itself. This effect was insensitive to the cholinergic antagonists. Thus, neuronal activity increased inositol phospholipid hydrolysis in a sympathetic ganglion rich in synapses, as well as in a sensory ganglion that contains few synapses. In the sympathetic ganglion, synaptic stimulation activated inositol phospholipid hydrolysis and this was primarily due to cholinergic transmission; both nicotinic and muscarinic pathways appeared to be involved.

Animals↗
PubMed1985

Neurophysiology and pharmacology of long-term potentiation in the rat sympathetic ganglion.

Brief tetanic stimulation of the preganglionic nerve induced a persistent potentiation of nicotinic synaptic transmission in the rat superior cervical sympathetic ganglion. Quantitative measurements of the post-tetanic increase in synaptic efficacy revealed two distinct time courses. The early, rapidly decaying component, termed post-tetanic potentiation (p.t.p.), had a decay time constant of 2-3 min, as reported elsewhere. The duration of the more persistent component, called long-term potentiation (l.t.p.), was extremely temperature dependent, lasting much longer at 32 degrees C than at 22 degrees C. In half of the experiments performed at 32 degrees C, l.t.p. showed no detectable decay over the course of 1 h or more after a brief tetanic stimulation. Other experiments were conducted at 22 degrees C. The induction of l.t.p. was dependent on the extracellular [Ca2+]. Transient elevation of the extracellular [K+] also produced a long-term enhancement of synaptic efficacy, and this effect was also Ca2+ dependent. The tetani that were effective in inducing l.t.p. (5-20 Hz for 5-20 s) were well within the physiological range of preganglionic activity. The magnitude and time course were related to frequency and duration of stimulation. The occurrence of l.t.p. was restricted to those preganglionic fibres that were tetanically stimulated. This lack of heterosynaptic or generalized effects was demonstrated by splitting the preganglionic nerve into two branches that could be independently tested and conditioned. Physiological activation of muscarinic or nicotinic receptors apparently does not play an essential role in causing ganglionic l.t.p., which is expressed as an enhancement of nicotinic transmission. A muscarinic antagonist (2 microM-atropine) did not block l.t.p. Preganglionic stimulation induced l.t.p. even when a high concentration of a nicotinic antagonist (3 mM-hexamethonium) was present during the tetanic stimulation. Furthermore, bath application of a cholinergic agonist (100-1000 microM-carbachol) could not substitute for tetanic stimulation in provoking l.t.p. Activation of adrenergic receptors also appeared not to play an essential role. Neither a beta-adrenergic antagonist (10 microM-sotolol or 1 microM-propranolol) nor an alpha-adrenergic antagonist (1 microM-phentolamine) had any significant effect on the magnitude or duration of l.t.p. The results indicate that ganglionic l.t.p. is a Ca2+- and temperature-dependent process that can be created independently of the activation of nicotinic, muscarinic or adrenergic receptors.

Action Potentials↗
PubMed1985

Long-term potentiation of synaptic acetylcholine release in the superior cervical ganglion of the rat.

The release of endogenous acetylcholine (ACh) from the in vitro rat superior cervical ganglion was measured by assaying the bathing medium. Simultaneously, synaptic transmission in the ganglion was assessed by recording post-ganglionic compound action potentials. A brief period of tetanic preganglionic stimulation (20 Hz for 20 s) induced a long-term potentiation of the post-ganglionic compound action potential. The same tetanic stimulation also consistently induced a long-term potentiation of stimulated ACh release. Spontaneous (non-stimulated) ACh release was not enhanced after tetanic stimulation. The content of ACh in the ganglion was not measurably increased after tetanic stimulation. These results suggest that the long-term increase in synaptic efficacy is due, at least in part, to an increase in the amount of ACh released by the afferent impulse.

Acetylcholine↗
PubMed1982

Cholinergic modulation of the release of [3H]acetylcholine from synaptosomes of the myenteric plexus.

The purpose of these experiments was to determine if cholinergic agents affected the release of acetylcholine (ACh) from a synaptosomal preparation of the guinea pig ileum myenteric plexus. The synaptosomal preparation was first incubated with the precursor [3H]choline; subsequently, release of the stored [3H]ACh was measured. The release was decreased by oxotremorine or exogenous ACh plus hexamethonium and increased by exogenous ACh plus evoked release that was inhibited by nicotinic antagonists or muscarinic agonists. Release was stimulated half-maximally by approximately 2 microM- and maximally by 10 microM-DMPP. Either in the absence of calcium or at 0 degrees C, DMPP was without effect. The effect of 10 microM-DMPP was brief, a significant stimulation occurring only within the first 2 min at 37 degrees C. Tetrodotoxin also inhibited excitation by DMPP but not completely. Thus, the release of [3H]ACh appears to be presynaptically modulated, negatively by muscarinic agonists and positively by nicotinic agonists.

Acetylcholine↗
PubMed1981

A synaptosomal preparation from the guinea pig ileum myenteric plexus.

Our interest in investigating the presynaptic modulation of acetylcholine release led to the development of a synaptosomal preparation from the guinea pig ileum myenteric plexus-longitudinal muscle. A crude synaptosomal fraction (P2) was obtained by homogenization and differential centrifugation. The preparation exhibited a specific uptake system for choline and for noradrenaline (NA), but not for 5-hydroxytryptamine (5-HT). Synaptosomes were isolated from this P2 fraction by an isoosmotic density gradient prepared from sucrose and metrizamide. The resultant synaptosomal fraction was enriched about sevenfold in both choline uptake and in choline acetyltransferase (ChAT). Choline was transported by a high-affinity system was a Km of 6.5 X 10(-7) M and a Vmax of 41 pmol/mg protein/min. Electron microscopy confirmed the synaptosomal nature of the gradient fraction. Some synaptosomal profiles contained only small, translucent vesicles whereas others also contained large (approx. 100 nm diameter) electron-opaque vesicles. The crude synaptosomal fraction synthesized acetylcholine (ACh) from exogenous choline and it released the synthesized ACh in a calcium-dependent manner.

Acetylcholine↗
PubMed1979

An approach to prediction of performance using behavioral and physiological variables.

10 male, middle-distance runners selected for their potential or actual success in running 1500 metres were subjected to laboratory tests of VO2 max and run time at 85% VO2 max. Using the Eysenck Personality Inventory (Eysenck, 1962), data were collected from the runners from which they were given a score on the Extraversion/Introversion dimension of personality. Pearson product-moment correlations were computed between 1500 m. run times and VO2 max, 85% utilization of VO2 max, and Extraversion scores. The highest correlation was between Extraversion and the 1500-m. run (r = .75). The multiple correlation between times for the 1500-m. run and Extraversion with VO2 max was .77. The results support the value of building comprehensive profiles for the athlete which include not only physiological and anatomical variables but behavioral measures as well.

Extraversion, Psychological↗
PubMedDate not supplied

Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo.

(2.4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a compound that interacts with rat neuronal nicotinic acetylcholine receptors (nAChRs), was evaluated using human recombinant nAChRs in vitro and various pharmacokinetic and behavioral models in rodents, dogs and monkeys. GTS-21 bound to human alpha 4 beta 2 nAChR (K1-20 nM) 100-fold more potently than to human alpha 7 nAChR, and was 18- and 2-fold less potent than (-)-nicotine at human alpha 4 beta 2 and alpha 7 nAChR, respectively. Functionally. GTS-21 stimulated [5H]dopamine release from rat striatal slices with an EC50 of 10 +/- 2 microM (250-fold less potent and 70% as efficacious as (-)-nicotine), an effect blocked by the nAChR antagonist dihydro-beta-erythroidine. However, GTS-21 did not stimulate human alpha 4 beta 2 nor human ganglionic nAChRs significantly. In vivo, GTS-21 had no adverse effect on dog blood pressure (< or = 2.5 micromol/kg i.v. bolus infusion), in marked contrast with (-)-nicotine, GTS-21 (-62 micromol/kg.s.e.) also did not cross-discriminate significantly with (-)-nicotine in rats and did not reduce temperature or locomotion in mice. Neither was it active in the elevated plus maze anxiety model (0.19-6.2 micromol/kg.IP) in normal mice. However, GTS-21 did improve learning performance of monkeys in the delayed matching-to-sample task (32-130 nmol/kg.i.m.).

Animals↗
PubMedDate not supplied

The role of neuronal nicotinic acetylcholine receptors in antinociception: effects of ABT-594.

ABT-594, a nicotinic acetylcholine receptor agonist, has antinociceptive effects in rat models of acute thermal, persistent chemical, and neuropathic pain. Direct injection of ABT-594 into the nucleus raphe magnus (NRM) is antinociceptive in a thermal threshold test and destruction of serotonergic neurons in the NRM attenuates the effect of systemic ABT-594. However, lidocaine-inactivation of the NRM prevents the antinociceptive effect of systemic (-)-nicotine but not that of systemic ABT-594.

Analgesics, Non-Narcotic↗