Biomedical subjects

T Crisp

Publications and source records attributed to T Crisp.

At least 37 records · Page 2Linked to original sources

PubMed1992

A single restraint stress exposure potentiates analgesia induced by intrathecally administered DAGO.

In rats, restraint exposure potentiates the magnitude and duration of analgesia following both the peripheral and intracerebroventricular administration of several opioid agonists as compared to non-stressed controls. It has been suggested that the site of action whereby restraint leads to potentiated opioid analgesia is located supraspinally. However, the possible contribution of spinal analgesic mechanisms also warrants investigation. Thus, the purpose of the present study was two-fold: (1) to determine whether a single exposure to restraint stress would result in the dose-dependent potentiation of analgesia following the intrathecal (i.t.) administration of the mu (mu)-receptor selective opioid agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) and (2) to quantify the degree of analgesia in restrained vs. non-restrained rats using the tail-flick and hot-plate analgesic assays. Using rats implanted with chronic i.t. cannula, dose- and time-course curves were observed following the i.t. administration of DAGO. The results demonstrate that both the duration and magnitude of analgesia was significantly potentiated in restrained rats compared to non-restrained controls. Restraint-treated rats receiving 0.15-0.6 micrograms of DAGO i.t. showed 1.3-1.5-fold potentiation of analgesia in the tail-flick assay and a 2.3-5.6-fold potentiation using the hot-plate assay. Restraint immobilization potentiated the magnitude and duration of DAGO-induced analgesia administered by the i.t. route as measured by the tail-flick and hot-plate assays. These data suggest that spinal analgesic mechanisms significantly contribute to the enhanced analgesic potency of opioids in subjects exposed to restraint stress.

Analgesics↗

PubMed1992

Sequence analysis and editing of the phosphoprotein (P) gene of rinderpest virus.

We have cloned the cDNA of the phosphoprotein (P) gene of the virulent (Kabete "O") strain of rinderpest virus and provided a comparative analysis of its sequence with that of the P genes of measles, canine distemper, and phocid distemper viruses. The gene encodes two overlapping open reading frames of 1521 and 531 nucleotides. Use of the first ATG would produce a P polypeptide of 507 amino acids with a calculated molecular weight of 54,344. The second ATG would produce a C polypeptide of 177 residues with a predicted molecular weight of 19,927. In addition, the insertion of a G residue at position 740 generates an alternative mRNA potentially encoding the V polypeptide of rinderpest virus. The homology comparisons in P amino acid sequences between rinderpest and measles, between rinderpest and canine distemper, and between rinderpest and phocid distemper viruses are 60, 44, and 46%, respectively. A four-way comparison shows an identity of 34%. Similar homology comparisons with the C amino acid sequence between rinderpest and measles, rinderpest and canine distemper, and rinderpest and phocid distemper viruses are 56, 42, and 40%, respectively. A homology of 31% is found in a four-way comparison for the C polypeptide. From the point of the insertion of the G residue, there is a homology of 78% between the V polypeptides of rinderpest and measle viruses.

Amino Acid Sequence↗

PubMed1992

The noradrenergic component contributing to spinal fentanyl-induced antinociception is supraspinally mediated.

1. Male Sprague-Dawley rats were fitted with intrathecal (i.t.) and intracerebroventricular (i.c.v.) catheters. Fentanyl was injected either i.t. or i.c.v., and the antinociceptive efficacy of fentanyl was evaluated using the tail-flick analgesiometric assay. 2. Fentanyl dose-dependently elevated tail-flick latency (TFL) following i.c.v. or i.t. administration. The antinociceptive effects of fentanyl were reversed by naltrexone. 3. Experiments were also designed to evaluate the effects of serotonin and alpha-adrenoceptor antagonists on i.t. or i.c.v. fentanyl-induced elevations in TFL. 4. Phentolamine administered i.t. reversed both the spinal and supraspinal antinociceptive effects of fentanyl, whereas i.t. methysergide did not significantly alter the i.t. or i.c.v. effects of the mu agonist. 5. These data suggest that fentanyl-induced antinociception does not rely on local serotonergic neuronal activation. Due to the highly lipophilic nature of fentanyl, it is possible that the noradrenergic component contributing to spinal fentanyl-induced analgesia is supraspinally-mediated.

Adrenergic Antagonists↗

PubMed1991

Evaluation of the interactions of serotonergic and adrenergic drugs with mu, delta, and kappa opioid binding sites.

Several serotonergic and adrenergic agents were tested for an ability to interact with mu, delta, and kappa opioid binding sites. Spiroxatrine interacted nearly equipotently with all three opioid subtypes, yielding Ki values near 110 nM. A number of other serotonergic and adrenergic agents interacted with affinities in the 1-50 microM range. Most of the other compounds tested in this study were found to compete for opioid binding to some degree, though not achieving a 50% inhibition of binding at concentrations up to 100 microM. If this interaction between monoaminergic agents and opioid receptors is found to have functional significance, it must be considered in the interpretation of results from studies using these agents to evaluate the contribution of monoaminergic systems to opioid-mediated events.

Animals↗

PubMed1991

The local monoaminergic dependency of spinal ketamine.

The effects of s.c. doses of naloxone, methysergide and phentolamine on ketamine-induced spinal analgesia were assessed to determine the involvement of opiate, serotonergic and noradrenergic components mediating ketamine's antinociceptive action. Ketamine administered intrathecally (i.t.) produced a significant elevation in tail-flick latency in rats. The spinal antinociceptive effects of ketamine were dose dependently reversed by methysergide (ID50 = 0.008 mg/kg s.c.), phentolamine (ID50 = 0.88 mg/kg s.c.) and naloxone (ID50 = 3.0 mg/kg s.c.). Unlike morphine, which remains analgesic and dependent on opiate interactions following bilateral lesions of the dorsolateral funiculus (DLF), ketamine analgesia was absent following DLF lesions. Thus, ketamine appears to produce an antinociceptive response which is dependent upon the neuronal activity of the descending pain-inhibitory pathways. The monoaminergic components comprising the descending pathways appear to be more prominent in the action of ketamine than they are in the spinal action of morphine. Furthermore, the spinal opioid receptors involved in ketamine's effect may be different from the mu subtype preferred by morphine.

Analgesia↗

PubMed1991

Serotonin contributes to the spinal antinociceptive effects of morphine.

This study was designed to determine if morphine administered intrathecally (IT) interacts with serotonergic or noradrenergic nerve terminals in the spinal cord to produce analgesia on the spinally mediated tail-flick test. Male Sprague-Dawley rats were fitted with IT catheters. One week later, animals were spinally pretreated with receptor antagonists selective for opioid, serotonin or alpha-adrenoceptors, and the ability of these agents to alter spinal morphine-induced antinociception was assessed. Morphine dose-dependently elevated tail-flick latency in a naltrexone-reversible manner. The serotonin receptor antagonists spiroxatrine (5-HT1A), pindolol (5-HT1B), ritanserin (5-HT2) and ICS 205-930 (5-HT3) attenuated the spinal analgesic effects of morphine. In contrast, the alpha 1 and alpha 2-adrenoceptor antagonists prazosin and yohimbine, respectively, did not alter morphine-induced elevations in tail-flick latency. These data substantiate earlier reports that spinal morphine-induced antinociception relies on an opioid receptor-mediated component in addition to a local serotonergic component. The finding that the alpha-adrenoceptor antagonists did not alter the antinociceptive effects of IT morphine suggests that spinal norepinephrine does not contribute to the analgesic effects of the opiate.

Adrenergic Antagonists↗

PubMed1991

Analgesic effects of serotonin and receptor-selective serotonin agonists in the rat spinal cord.

1. Serotonin (5-HT) and selective 5-HT receptor agonists were administered intrathecally (i.t.) in rats, and the antinociceptive efficacy of these agents was assessed on the tail-flick and hot plate tests. 2. The 5-HT receptor agonists examined in this study included the 5-HT1A agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), the 5-HT1B agonist m-trifluoromethylphenylpiperazine (TFMPP), the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT3 agonist phenylbiguanide (PBG). 3. None of these agents produced significant elevations in tail-flick latency (TFL) at doses which produced elevations in hot plate latency (HPL). 4. In contrast, the i.t. dose of 5-HT which elevated TFL also produced analgesia on the hot plate test. 5. Serotonin-induced elevations in TFL were reversed by pindolol, ritanserin and ICS 205-930, suggesting that 5-HT interacts with more than one 5-HT site in the spinal cord to produce analgesia on the tail-flick test. 6. The finding that ritanserin reversed 5-HT-induced elevations in HPL suggests that the 5-HT2 site is primarily responsible for mediating the spinal antinociceptive effects of 5-HT on the hot plate test.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1989

Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family.

Using applications of the polymerase chain reaction (PCR) technique, cDNA clones have been isolated encoding bovine vascular endothelial growth factor (VEGF), a mitogen with specificity for vascular endothelial cells. Analysis of the clones indicates that VEGF can exist in two forms, probably due to alternative RNA splicing. The amino acid sequences predicted from the clones also show that VEGF shares homologies of about 21% and 24% respectively with the A and B chains of human platelet-derived growth factor (PDGF), and has complete conservation of the eight cysteine residues found in both mature PDGF chains. The homology is not reflected in function, however, since the cell types responsive to VEGF are distinct from those responsive to homo- and heterodimers of the PDGF chains.

Amino Acid Sequence↗

PubMed1989

Cricket: fast bowler's back and thrower's shoulder.

Preventive measures are important in cricket. Although not associated with as high an incidence of injury as contact sports, sudden bursts of extreme exertion after long periods of inactivity in cricket carry their own morbidity.

Athletic Injuries↗

PubMed1989

Spinal beta-endorphin analgesia involves an interaction with local monoaminergic systems.

beta-Endorphin administered intrathecally (i.t.) in rats produced a dose-dependent elevation in tail-flick latency. Naltrexone administered i.t. as a pretreatment reversed the spinal antinociceptive action of beta-endorphin, suggesting that the opioid interacts directly with spinal opiate receptors. Spinal administration of the alpha 1-adrenoceptor antagonist WB-4101 failed to alter the analgesic effects of the opioid, whereas the alpha 2-adrenoceptor antagonist yohimbine completely blocked beta-endorphin-induced elevations in tail-flick latency. Thus, there is an apparent specificity for the alpha 2-adrenoceptor to mediate the spinal action of beta-endorphin. The 5-HT1 and 5-HT3 receptor antagonists (spiroxatrine and ICS 205-930, respectively) also reversed the analgesic effects of the opioid, while the 5-HT2 receptor antagonist ritanserin only partially blocked beta-endorphin-induced elevations in tail-flick latency. The present results suggest that beta-endorphin produces analgesia at the spinal level via an opiate receptor-mediated interaction with spinal monoaminergic nerve terminals.

Adrenergic alpha-Antagonists↗

PubMed1989

A local serotonergic component involved in the spinal antinociceptive action of morphine.

Participation of opiate, serotonergic and noradrenergic components in the antinociceptive action of intrathecally administered morphine was evaluated by measuring the ability of subcutaneously administered doses of naloxone, methysergide and phentolamine to alter analgesia. Morphine produced a dose-dependent elevation of the tail-flick latency, due exclusively to local spinal actions. For example, 10 nmol of the drug, when administered intrathecally in rats with bilateral lesions of the dorsolateral funiculus, produced an increase in the tail-flick latency, that was similar to that observed in intact animals. Furthermore, morphine was ineffective when administered intracerebroventricularly into the fourth ventricle of intact rats. The spinal antinociceptive action of the opiate was antagonized by naloxone (ID50 = 0.035 mg/kg, s.c.) but was also significantly attenuated by methysergide (ID50 = 4.28 mg/kg, s.c.). Phentolamine was ineffective. Doses of methysergide that were most effective in reversing the spinal action of morphine also produced hyperalgesia when administered alone. On the other hand, when the dorsolateral funiculus was lesioned, the hyperalgesia was no longer observed, yet the antagonist remained effective against morphine. These data suggested that the doses of methysergide needed to antagonize the action of morphine were in the same range as those needed to block the synaptic actions of serotonin (5-HT) released from the tonically-acting, descending pain inhibitory nerves. The results demonstrate that local opiate, as well as serotonergic, mechanisms mediate the antinociceptive action of morphine in the spinal cord. The recruitment of a serotonergic component may be related to an action of opiates within the spinal cord, to cause the release of serotonin from the terminal fields of the spinipetal serotonergic nerves.

Analgesics↗

PubMed1989

The antinociceptive effects of 3,4-methylenedioxymethamphetamine (MDMA) in the rat.

The antinociceptive effects of MDMA and morphine were examined in rats using the tail-flick and hot-plate analgesiometric tests. MDMA, in the dose range of 1.5-6.0 mg/kg IP, produced a dose-dependent elevation in hot-plate latency, but did not elevate tail-flick latency. In contrast, morphine (2-8 mg/kg, IP) produced analgesia on both the tail-flick and hot-plate tests in a dose-dependent manner. Neither the opiate antagonist naltrexone nor the adrenoceptor antagonist phentolamine effectively attenuated MDMA-induced analgesia. Conversely, the serotonin antagonist methysergide significantly reversed the analgesic effects of MDMA on the hot-plate test. These findings suggest that the antinociceptive effects of MDMA are serotonergically mediated. Furthermore, the results verify earlier findings describing the test-specific effects of serotonin-induced pain modulation.

3,4-Methylenedioxyamphetamine↗

PubMed1988

The mu opiate receptor is responsible for descending pain inhibition originating in the periaqueductal gray region of the rat brain.

Opiate agonists exhibiting selectivity for mu, kappa, sigma, and delta opiate receptors were microinjected into the periaqueductal gray region (PAG) of the brain of rats to determine the receptor subtype(s) associated with the initiation of descending pain inhibition. The spinally organized, heat nociceptive tail-flick reflex was used to detect analgesia. Only morphine (mu) and [D-Ala2,D-Leu5]enkephalin (DADLE) (delta greater than mu) produced analgesia. However, both drugs appeared to be acting through the mu (morphine) receptor, since: (1) the action of DADLE was not inhibited by delta receptor antagonists, (2) a more highly selective delta agonist [D-Pen2,D-Pen5]enkephalin was ineffective and (3) agonists selective at other non-mu receptor sites (ethylketocyclazocine and U50,488H for kappa; n-allylnormetazocine for sigma) were also ineffective. It appeared that DADLE might be acting as a partial agonist at the morphine receptor in the PAG. The peptide was an agonist with low efficacy, and when a maximally effective dose of the peptide was administered simultaneously with morphine antagonism was observed. Ethylketocyclazocine and n-allylnormetazocine were also found to antagonize morphine, an observation that is consistent with the suggestion that they may act as mu receptor antagonists in addition to their agonistic action at kappa and sigma receptors, respectively. Thus, mu receptors appear to be responsible for the spinopetal analgesia from the PAG of the rat.

Animals↗

PubMed1988

Cloning and sequence analysis of the hemagglutinin gene of the virulent strain of rinderpest virus.

We have cloned the cDNA of the hemagglutinin (HA) gene of the virulent (Kabete O) strain of rinderpest virus and produced a comparative analysis of its sequence with that of the HA genes of rinderpest (lapinized strain) and measles viruses. The gene has an open reading frame of 1827 nucleotides, and the derived protein is 609 amino acids long with a calculated molecular weight of 68,006. The Kabete O HA polypeptide is identical in length to the HA of the lapinized strain of rinderpest virus and has a similar hydropathy profile. The nucleotide divergence between the lapinized and the Kabete O HA genes is 11.4% within the coding region, and 34.3% in the 3' untranslated region. The two rinderpest HA polypeptides differ at 74 amino acid residues for a divergence of 12.2%. Three-way comparison of the two rinderpest HA molecules with the measles virus HA polypeptide indicates that 56.6% of the residues are conserved.

Amino Acid Sequence↗

PubMed1987

Structural comparison of human apolipoproteins B-48 and B-100.

In this study we have investigated the structural relationship between human apolipoproteins B-48 and B-100 by comparing protein structure and by comparing nucleotide sequence from intestinal and hepatic cDNA clones. Sequences from intestinal and hepatic cDNA were identical over the entire distance analyzed (7194 bases), which is more than required to code for B-48. The amino-terminal amino acid sequences from intact B-48 and B-100 proteins were also identical over the entire distance analyzed (16 residues). Additional protein homology was evaluated by the combined techniques of peptide mapping and immunoblotting. Purified B-48 and B-100 were each digested with three different endoproteases, and the resulting peptides were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Peptide bands were then detected by silver stain and by Western blotting with antisera against specific regions of B-48 and B-100. The resulting patterns suggest that B-48 is extensively homologous with the amino-terminal portion of B-100. We have identified only four peptides from B-48 (at least one in each digest) that are absent from the parallel digests of B-100. These peptides appear to arise from the ultimate carboxyl terminus of B-48 and appear to be totally homologous with a region located near the center of B-100. Our observations suggest that mature, circulating B-48 is homologous over its entire length (estimated to be between 2130 and 2144 amino acid residues) with the amino-terminal portion of B-100 and contains no sequence from the carboxyl end of B-100.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1987

Properties of the interaction between ketamine and opiate binding sites in vivo and in vitro.

Analgesia induced by ketamine appears to be partially mediated by opiate mechanisms. Not only is its action attenuated by the narcotic antagonist naloxone, but the drug has a weak affinity for, and interacts stereoselectively at, opiate receptors. It also produces a classical narcotic action on the guinea-pig ileum. The present study showed that analgesic doses of the drug in rats yielded concentrations sufficient to interact effectively at opiate binding sites in vivo. A dose-dependent (80-120 mg/kg i.p.) inhibition of the binding of [3H]naloxone was observed in both brain and spinal cord. All regions of the brain (except the cerebellum) were affected, but the reduction was significant in the cortex, hippocampus, thalamus and striatum. Thus, a component of ketamine-induced analgesia could be related to a functional interaction with opiate receptors. Additionally, ketamine may be similar to morphine in its preference for the mu, rather than the delta sub-type of opiate receptors, and thus may promote mu-mediated pharmacological effects. For example, in vitro studies of radioligand binding showed that ketamine and morphine were four times more effective in inhibiting the binding of [3H]dihydromorphine than that of [3H] [D-Ala2, D-Leu5] enkephalin. On the other hand, ketamine also effectively interacted at a component of the sigma opiate/phencyclidine binding sites that appears to be relatively insensitive to morphine. This component may be involved in dysphoria induced by ketamine.

Animals↗

PubMed1986

Do serotonin-containing dorsal raphe neurons possess autoreceptors?

The potential role of autoreceptors in regulating the activity of serotonin-containing dorsal raphe (RD) neurons was examined by recording the activity of these neurons under a variety of conditions both in vivo and in vitro in the mouse. RD neurons recorded in vivo displayed the characteristic slow, rhythmic discharge pattern previously described for rat and cat RD cells. The activity of these neurons was suppressed in a dose-dependent manner by tryptophan, LSD and chlorimipramine administered intravenously. The inhibitory effect of tryptophan and chlorimipramine was abolished by pretreatment with p-chlorophenylalanine, while that of LSD was not. There were no significant changes in the spontaneous discharge rate of raphe neurons over time when recorded in vitro, even though tissue serotonin and its metabolite, 5-hydroxyindoleacetic acid, decreased dramatically. Prior depletion of brain serotonin by p-chlorophenylalanine administration resulted in no significant change in RD neuron activity recorded in vitro. Elevation of brain serotonin by monoamine oxidase inhibition produced a total suppression of raphe cell activity in vitro. Similarly, increasing the concentration of serotonin in the tissue slice by adding serotonin directly to the incubation medium resulted in a profound, though transitory, depression of RD neuron activity. This depressant effect of serotonin was rapidly reversible upon drug wash-out. Serotonin receptor blockers, methiothepin, cyproheptadine and methysergide produced no significant change in RD cell activity. The 5HT reuptake blocker, fluoxetine, produced a total suppression of RD neuron activity in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1985

Chronic administration of D-amphetamine increases [3H]spiroperidol binding in cat brain.

Administration of D-amphetamine sulfate twice daily for 10 consecutive days, in doses increasing from 10 mg/kg per day (i.p.) to 30 mg/kg per day resulted in significant increases in the Bmax for [3H]spiroperidol receptor binding in the striatum (+44.7%) and limbic forebrain (+40.3%) in cats. There were no significant changes in the KD value for either brain region. A single dose of amphetamine (15 mg/kg i.p.) produced no significant changes in [3H]spiroperidol binding in either brain region. These data are in contrast with previous studies which reported a significant decrease in dopamine receptor binding following chronic amphetamine treatment in rats.

Animals↗