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H J Cooke

Publications and source records attributed to H J Cooke.

At least 91 records · Page 5Linked to original sources
PubMed1992

Neurokinin 1 receptors mediate substance P-induced changes in ion transport in guinea-pig ileum.

Tachykinin receptors mediating substance P-induced secretion were examined in muscle-stripped segments of guinea-pig ileum set up in flux chambers. Changes in the short-circuit current (Isc) served as an index of active, electrogenic ion transport. Substance P evoked a transient increase in Isc which was concentration-dependent. The maximal change in Isc occurred at 1 microM concentration. [Sar9,Met(O2)11]-substance P, a neurokinin 1 (NK-1) receptor agonist, evoked a similar concentration-dependent increase in Isc. [Nle10]NKA(4-10) (1 microM) or [Pro7]NKB (1 microM), selective NK2 and NK3 agonists, respectively, had minimal effects on Isc. CP-96,345 (5 microM), a nonpeptide NK-1 antagonist, and the peptide NK-1 antagonist, GR82334 (1 microM), reduced the secretory response to substance P (50 nM) in the presence and absence of tetrodotoxin (0.2 microM). The NK2 antagonist, [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10) MEN 10207 had no effect on the substance P response. Tetrodotoxin (0.2 microM) significantly reduced, but did not abolish the Isc response to substance P (1 microM) and [Sar9,Met(O2)11]substance P (1 microM). The substance P response was unaltered by 5 microM atropine and 50 microM mecamylamine. Piroxicam (10 microM) or pyrilamine (10 microM) or a combination of both had no effect on the tetrodotoxin-resistant substance P response. Electrical field stimulation evoked a biphasic increase in Isc which was significantly reduced by 0.2 microM tetrodotoxin. Atropine (5 microM) reduced the first peak of the biphasic response and mecamylamine (50 microM) had no effect. Similarly, 5 microM CP-96,345 and 1 microM GR82334 did not alter the EFS-induced change Isc. The results suggest that substance P-evoked secretory responses are independent of histamine or prostaglandins. Substance P responses are mediated by an NK-1 receptor type on enteric neurons and possibly epithelial cells.

Animals↗
PubMed1992

Loss of absorptive capacity for sodium and chloride in the colon causes diarrhoea in Potomac horse fever.

Ehrlichia risticii, an obligate intracellular bacterium in the family Rickettsiaceae, causes Potomac horse fever which is often associated with severe watery diarrhoea. The mechanism of the diarrhoea is unknown. The aim of this study was to determine whether sodium and chloride transport, morphology and cyclic adenosine 3', 5'-monophosphate (cyclic AMP) content of colonic mucosa was altered in E risticii-infected horses. Mucosa-submucosa sheets from the large and small colon of nine infected and seven to nine uninfected horses were set up in Ussing chambers for measurement of short-circuit current and transepithelial 22Na and 36Cl fluxes. Uninfected tissues absorbed both sodium and chloride whereas absorption of sodium and chloride was abolished in infected tissues. Bethanechol and histamine evoked a concentration-dependent increase in short-circuit current in both groups, but the responses were attenuated at all concentrations in infected horses. Slight focal degeneration of colonic epithelial cells and loss of microvilli from glandular epithelial cells occurred in infected horses. There was a significant increase in cyclic AMP content in colonic mucosa of infected animals. The results suggest that E risticii infection induces focal microscopic degeneration of epithelial cells and an increase in intracellular cyclic AMP in colonic mucosa. These alterations are associated with malabsorption of sodium and chloride and could cause diarrhoea.

Animals↗
PubMed1992

Telomere-associated chromosome fragmentation: applications in genome manipulation and analysis.

Telomere-associated chromosome fragmentation (TACF) is a new approach for chromosome mapping based on the non-targeted introduction of cloned telomeres into mammalian cells. TACF has been used to generate a panel of somatic cell hybrids with nested terminal deletions of the long arm of the human X chromosome, extending from Xq26 to the centromere. This panel has been characterized using a series of X chromosome loci. Recovery of the end clones by plasmid rescue produces a telomeric marker for each cell line and partial sequencing will allow the generation of sequence tagged sites (STSs). TACF provides a powerful and widely applicable method for genome analysis, a general way of manipulating mammalian chromosomes and a first step towards constructing artificial mammalian chromosomes.

Animals↗
PubMed1992

Beginning or end? Telomere structure, genetics and biology.

The word telomere derives from the Greek word telos meaning 'end', roughly translating as 'the thing at the end' when the end is that of a chromosome. Telomeres belie their apparent simplicity of structure by being involved in a wide range of diverse biological phenomena. Much of our understanding of telomere behaviour comes from studies in lower eukaryotes such as ciliates and yeast, the subject of many recent reviews. Here we concentrate on the mammalian telomere, recent progress in its study, and how recent evidence for an involvement of telomeres in the regulation of gene expression and DNA replication in yeast points to new aspects of mammalian telomere function yet to be explored.

Animals↗
PubMed1992

Acetylcholine release from colonic submucous neurons associated with chloride secretion in the guinea pig.

Electrical field stimulation of submucous neurons in the guinea pig distal colon evokes an increase in chloride secretion sensitive to cholinergic blockade. This study was undertaken in the guinea pig to determine the feasibility of measuring acetylcholine (ACh) release simultaneously with ion transport in sheets of colonic submucosa/mucosa set up in flux chambers modified for perfusion of the submucosal surface. Release of [3H]ACh was determined in the absence of cholinesterase inhibitors as the stimulus-evoked outflow of 3H from preparations preloaded with [3H]choline. [3H]ACh released in response to electrical stimulation correlated with short-circuit current at frequencies from 0.5 to 10 Hz. At 5 and 10 Hz, the stimulus-evoked release of [3H]ACh decreased during subsequent stimulation periods. The stimulus-evoked increase in [3H]ACh was attenuated by tetrodotoxin. [3H]ACh release evoked at stimulus frequencies of 0.5-10 Hz was not altered by atropine despite a reduction in short-circuit current. This study illustrates the feasibility of measuring ACh release simultaneously with ion transport in flux chambers. The results provide new information on the response characteristics of colonic submucous neurons and provide direct evidence for regulation of chloride secretion by ACh.

Acetylcholine↗
PubMed1992

Submucosal reflexes: distension-evoked ion transport in the guinea pig distal colon.

Muscle-stripped segments of distal colon from guinea pigs were mounted in modified flux chambers to determine the effect of distension on mucosal secretion. Ion secretion was monitored as changes in short-circuit current (Isc). Distending forces were pressure gradients established by controlled reduction in liquid volume of the submucosal compartment of the chamber. Volume removal for 10 s or 5 min evoked a monophasic or biphasic increase in Isc, which returned to baseline within 5-20 min. The amplitude of the response correlated with the volume removed and was reduced by bumetanide and Cl-free solutions but not by tetraethylammonium or amiloride. Tetrodotoxin and atropine also suppressed the response. Neither the nicotinic receptor antagonist mecamylamine, the 5-hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205-930, or the prostaglandin synthesis inhibitor piroxicam altered the response. Addition of prostaglandin D2 to the submucosal bath significantly enhanced the response. The results suggest that distension of the colon evokes anion secretion by activation of reflex circuits with cholinergic neurons and muscarinic synapses. Prostaglandins and 5-hydroxytryptamine acting at 5-HT3 receptors appear not to be signal substances in the reflex pathway, which evokes the secretory response to distension.

Animals↗
PubMed1992

Neuroimmune interactions: role for cholinergic neurons in intestinal anaphylaxis.

The role of cholinergic neurons in mediating chloride secretion in anaphylaxis was assessed in muscle-stripped segments of distal colon from guinea pigs immunized to bovine milk. beta-Lactoglobulin evoked a concentration-dependent increase in short-circuit current (Isc) in immune, but not nonimmune, tissues. The Isc response to beta-lactoglobulin was reduced by piroxicam, pyrilamine, and cimetidine. Tetrodotoxin and atropine reduced the Isc response to beta-lactoglobulin in immune animals, whereas mecamylamine and ICS 205-930 were ineffective. beta-Lactoglobulin evoked a concentration-dependent increase in acetylcholine (ACh) release in immune, but not nonimmune, animals. In immune tissues after challenge with beta-lactoglobulin, ACh release paralleled the change in Isc. Piroxicam, cimetidine plus pyrilamine, or a combination of piroxicam, cimetidine, and pyrilamine significantly reduced the release of ACh after beta-lactoglobulin challenge. Histamine, dimaprit, and prostaglandins E2 evoked an increase in ACh release. These results suggest that beta-lactoglobulin releases prostaglandins and histamine probably from mast cells. Secretory responses that occur when immune animals are challenged with beta-lactoglobulin result, in part, from activation of cholinergic neurons that utilize muscarinic synapses for transfer of signals to the epithelium.

Acetylcholine↗
PubMed1992

Intestinal secretion after jejunal bypass in the ground squirrel.

The preceding paper [H. V. Carey, Am. J. Physiol. 263 (Regulatory Integrative Comp. Physiol. 32): R1202-R1208, 1992] demonstrated that a 3-day fast or the extended fast of hibernation enhanced the chloride secretory responses to a variety of agonists in the ground squirrel jejunum. Here we examined the effect of jejunal bypass on intestinal secretory capacity in squirrels that either remained active and continued to feed (ACT), or were induced to hibernate (HIB). Mucosal wet weights were reduced in jejunal segments that had little or no exposure to the luminal stream (all segments from HIB and bypassed segments from ACT) compared with segments in contact with luminal contents (sham and in continuity segments of ACT). Tissue conductances were greater in those segments not exposed to luminal contents. Short-circuit current (Isc) responses to electrical stimulation of submucosal neurons, or to serosal carbachol, were greater in segments not exposed to luminal contents when responses were normalized to serosal surface area. Normalization of secretory responses to crypt area produced a similar pattern. Isc responses to mucosal alanine, which reflect electrogenic Na+ absorption, were greatest in segments with little or no exposure to luminal contents. Tissue wet weights, conductances and secretory responses of bypassed segments of HIB and ACT squirrels were always similar. These results suggest that luminal contents directly influence jejunal secretory capacity.

Alanine↗
PubMed1991

Thyrotropin-releasing hormone excites submucous neurons in guinea-pig ileum.

Actions of thyrotropin-releasing hormone (TRH) on submucous neurons of the guinea-pig ileum were examined with intracellular electrophysiological methods. TRH evoked excitatory responses in S/type 1 and AH/type 2 neurons. The responses consisted of slowly activating membrane depolarization, augmented excitability and an increase in input resistance that resulted from a decrease in potassium conductance. The results suggest a neuromodulatory/neurotransmitter function for TRH.

Animals↗
PubMed1991

Mouse minor satellite DNA genetically maps to the centromere and is physically linked to the proximal telomere.

As an adjunct to attempts to define functionally important sequences at human centromeres, we have undertaken a long-range physical analysis of these regions in the mouse. Mouse centromeres are usually situated very close to the chromosome ends and are closely associated with minor satellite sequences on the basis of cytological observations. Using pulsed-field gel electrophoresis we find that this satellite DNA is arranged as tandem arrays, predominantly uninterrupted by nonsatellite sequences. These arrays can be released largely intact by digestion with a range of enzymes that generally cleave frequently in non-satellite DNA. The restriction fragments carrying these arrays are polymorphic in size between inbred strains and provide direct markers for mouse centromeres. To illustrate the possible use of these polymorphic markers we have mapped a 1.3-Mb PvuII variant in a set of RI strains to the centromere of Chromosome 7. The minor satellite arrays are very close to the centromeric telomere and physical linkage with terminal repeat sequences can readily be detected, placing many minor satellite arrays on terminal restriction fragments smaller than 1 Mb. The apparent lack of any sizable amount of nonsatellite DNA between the minor satellite and the terminal repeat arrays indicates that many mouse chromosomes are truly telocentric.

Alleles↗
PubMed1991

In vivo loss of telomeric repeats with age in humans.

Telomeric DNA in the skin cells of 21 human subjects aged between 0 and 92 years was quantified by determining the length of the telomeric smear and the relative amount of TTAGGG repeat sequences. Both telomere length and quantity of telomeric repeat sequences were found to decrease significantly with age. Telomere loss has previously been postulated to be a caused of cell senescence.

Adolescent↗
PubMed1991

Neuroimmune regulation of colonic secretion in guinea pigs.

The role of submucosal neurons in anaphylactic-like responses in colonic epithelium from immunized guinea pigs was examined 6-8 wk after inoculation with 2 x 10(3) infective Trichinella spiralis larvae. Serosal addition of T. spiralis antigen (20 micrograms/ml) to muscle-stripped segments of colon set up in flux chambers evoked a maximum increase in short-circuit current within 5 min in immune, but not nonimmune, guinea pigs. Quercetin, a membrane-stabilizing drug, and pyrilamine, a histamine H1 receptor antagonist, attenuated epithelial responses evoked by T. spiralis antigen. Antigen-induced epithelial responses were reduced by neural blockade with tetrodotoxin and by the muscarinic receptor antagonist atropine but not by blockade of nicotinic receptors with mecamylamine. Antigenic challenge of colonic mucosa from immune guinea pigs enhanced the secretory responses to endogenously released neurotransmitters evoked by electrical field stimulation and substance P. In the presence of antigen, the tetrodotoxin-insensitive component of the carbachol response was enhanced and was reversed by quercetin but not pyrilamine. The results suggest that submucosal cholinergic nerves play a role in mediating the rapid epithelial responses evoked by worm antigen in the colonic mucosa of T. spiralis-immune guinea pigs. Interaction of immunological mediators with neurotransmitters in the submucosal plexus augments the secretory mucosal response triggered by T. spiralis in immunized hosts.

Animals↗
PubMed1991

Electrophysiological properties of neurons in submucosal ganglia of guinea pig distal colon.

Intracellular recording methods were used in vitro to study the electrophysiological behavior of neurons in ganglia of the submucosal plexus in the distal colon of the guinea pig. The results revealed subpopulations of submucosal ganglion cells that corresponded to the AH/type 2, S/type 1, type 3, and type 4 subpopulations found elsewhere in the intestine. Electrical behavior of colonic submucosal neurons differed from the myenteric plexus of the colon, rectum, and stomach and the small intestinal submucosal plexus mainly in the relative proportions of the different subpopulations. Regional differences in this respect may be a reflection of functional specialization in the diverse regions of the alimentary canal.

Action Potentials↗
PubMed1991

Synaptic transmission in submucosal ganglia of guinea pig distal colon.

Intracellular electrical recording was used to investigate synaptic behavior of ganglion cells in the neural networks of the submucosal plexus of the guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs), mediated by nicotinic receptors, were found in all S/type 1 neurons, 70% of AH/type 2, 75% of type 3, and 95% of type 4 neurons. Slow EPSPs were characterized by membrane depolarization, increased input resistance, enhanced action potential discharge, and suppression of hyperpolarizing afterpotentials in 64% of the S/type 1 neurons, 74% of AH/type 2, 31% of type 3, and 70% of type 4 neurons. Micropressure application of acetylcholine evoked a two-component depolarizing response consisting of an initial transient with decreased input resistance followed by a prolonged depolarization associated with increased input resistance. The transient response was suppressed by nicotinic-blocking drugs. Muscarinic antagonists suppressed the prolonged response. Acetylcholine acted also at presynaptic muscarinic receptors to suppress stimulus-evoked fast EPSPs. No stimulus-evoked inhibitory synaptic potentials were observed. Norepinephrine, applied by microejection, acted at alpha 2-adrenoceptors to hyperpolarize the membrane potential in association with decreased neuronal input resistance.

Acetylcholine↗
PubMed1991

Effect of hibernation and jejunal bypass on mucosal structure and function.

Intestinal mucosal structure and function may be regulated by systemic factors associated with oral feeding, as well as local responses initiated by contact of the mucosa with food. This study compared the relative effects of these factors in an animal model that undergoes seasonal long-term fasting. Jejunal bypass operations or sham surgeries were performed on active fed ground squirrels or on squirrels that subsequently ceased feeding and hibernated. Mucosal wet weight, protein content, villus height, and surface area were reduced in jejunal segments that had minimal exposure to luminal contents (bypassed segments of active squirrels and all segments of hibernators) compared with segments exposed to the luminal stream (incontinuity and sham segments of active squirrels). When normalized to mucosal weight, transepithelial absorption of 3-O-methylglucose and alanine-dependent sodium flux were greater in jejunal segments with minimal exposure to luminal nutrients. Altered structure in bypassed segments of active and hibernating squirrels paralleled changes in functional parameters despite the presence of different systemic factors in the two groups. Thus, in this animal model, contact of the mucosa with food, and not systemic factors associated with oral feeding, is the primary factor maintaining mucosal mass. The absence of mucosal contact with nutrients enhances specific absorptive function by mechanisms that have yet to be determined.

3-O-Methylglucose↗
PubMed1991

Neural 5-hydroxytryptamine receptors regulate chloride secretion in guinea pig distal colon.

The effects of 5-hydroxytryptamine (5-HT) on epithelial short-circuit current (Isc) were determined and related to the 5-HT effects on electrical and synaptic behavior of neurons in the submucosal plexus of the guinea pig colon. 5-HT evoked a biphasic increase in Isc that was reduced by bumetanide, Cl(-)-free solutions, atropine, and mecamylamine and abolished by tetrodotoxin. The 5-HT response was mimicked by 2-methyl-5-HT, but not by 5-hydroxyindalpine, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, and 5-methoxytryptamine (5-MeOT). ICS 205-930 suppressed the 5-HT response. Electrical field stimulation of submucosal neurons evoked an increase in Isc indicative of Cl- secretion that was reduced by 5-MeOT and enhanced by 2-methyl-5-HT. Application of 5-HT to submucosal neurons by micropressure ejection resulted in membrane depolarization, augmented excitability, and repetitive spike discharge. The depolarization was biphasic, consisting of rapidly and slowly activating components. The rapidly activating component was suppressed by ICS 205-930. Fast excitatory postsynaptic potentials evoked by electrical stimulation of interganglionic connectives were suppressed by 5-HT and 5-MeOT. These results suggest that 5-HT activates 5-HT3 receptors, which mediate fast excitatory responses in submucosal neurons, leading to release of acetylcholine at nicotinic and muscarinic synapses and stimulation of Cl- secretion. Presynaptic inhibition suppresses acetylcholine release and results in attenuation of neurally evoked Cl- secretion.

Animals↗
PubMed1991

Serotonin receptors on submucous neurons in guinea pig colon.

Intracellular microelectrodes were used to investigate the neuropharmacology of 5-hydroxytryptamine (5-HT) in the submucous plexus of the distal colon of the guinea pig. Three effects resulted from application of 5-HT to submucous neurons. Two of the effects were components of a biphasic depolarization mediated by receptors on the neuronal cell body. The third was suppression of acetylcholine release at nicotinic synapses on the cell bodies and was mediated by presynaptic 5-HT receptors. The initial component of the biphasic depolarization was a rapidly activating response characterized by increased ionic conductance and a tendency for rapid desensitization. Pharmacological analysis with selective agonists and antagonists suggested mediation of this response by the 5-HT3 receptor subtype. The second component of the depolarizing response was a slowly activating and long-lasting depolarization associated with decreased ionic conductance. Analysis of this response suggested it was mediated by the 5-HT1P receptor subtype. Identification of the presynaptic receptors for 5-HT was equivocal. These receptors did not behave like 5-HT3 or 5-HT1P receptor subtypes. The putative 5-HT4 agonist 5-methoxytryptamine was equipotent with 5-HT in producing presynaptic inhibition at the fast nicotinic synapses.

Analysis of Variance↗