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Biomedical subjects

M E Hall

Publications and source records attributed to M E Hall.

At least 37 records · Page 2Linked to original sources
PubMed1981

Minimum structure opioids-dipeptide and tripeptide analogs of the enkephalins.

Through a systematic reduction of peptide structure, a series of 25 tripeptide and 5 dipeptide amide and alcohol analogs of enkephalin were synthesized and assayed in vitro on the stimulated guinea pig ileum. Tyr-Pro-Phe-NH2, Tyr-D-Ala-Phe-NH2, Tyr-D-Ala-Phe-ol and Tyr-D-Phe-Phe-NH2 had 20-25% the potency of Met-enkephalin. Four aromatic alkylamides of the dipeptide Tyr-D-Ala were made with benzylamine, phenethylamine, phenylpropylamine and phenylbutylamine. All had full naloxone reversible enkephalin-like activity in the ileum assay. Tyr-D-Ala-phenylpropylamide has about 80% the potency of Met-enkephalin in vitro, and is equipotent with Tyr-D-Ala-Gly-Phe-Met-NH2 in producing analgesia in mice after intraventricular administration. Tyr-D-Phe-NH2 is the smallest peptide to show full intrinsic enkephalin-like activity in vitro, although its potency is very low.

Animals↗
PubMed1978

Two-dimensional gel electrophoresis of proteins in rapid axoplasmic transport.

Two-dimensional electrophoresis of proteins has allowed high resolution analysis of the protein species rapidly transported in the frog sciatic nerve. The 7th, 8th and 9th dorsal root ganglia were selectively labeled with [3H]leucine or [35S]methionine in one compartment of a lucite chamber. Transport of TCA-precipitable material was monitored in the spinal roots and sciatic nerve kept in another compartment. Fastest transport rates were 75-90 mm/day at 18 decrees C. Ligation of the nerve 30 mm distal to the 8th ganglion at the beginning of the experiment resulted in accumulation of label during a 24 h period. This material was subjected to two-dimensional electrophoresis (pI 5-8; mol.wt. 10(4)-10(5) daltons) in 3 mm nerve segments. Autoradiographs or fluorographs from segments proximal to the ligature yielded a pattern of about 140 spots. Of these, at least 60 were considered to be independent protein species. Neither actin nor tubulin were present among these rapidly-transported, labeled proteins. No pattern was observed from segments distal to the ligature. Blocking protein synthesis with 18 micrometer anisomycin reduced the accumulation of label proximal to the ligature by 98%. Direct labeling of nerve segments produced patterns significantly different from the pattern of transported proteins.

Animals↗
PubMed1978

Changes in synthesis of specific proteins following axotomy: detection with two-dimensional gel electrophoresis.

Changes in protein synthesis during development and following axotomy were analyzed by two-dimensional gel electrophoresis. The two major postganglionic nerves emerging from the superior cervical sympathetic ganglia (SCSG) of adult rats were either cut or crushed unilaterally. At intervals ranging from 1 to 112 days after surgery both SCSG were removed and incubated for 1 hr in the presence of 14C-leucine. Proteins were extracted and subjected to two-dimensional electrophoretic separation and autoradiography. With this technique, proteins are separated on the basis of isoelectric point and molecular weight. Also, intact SCSG from 1, 2, 7, and 14 day old rats were labeled and analyzed. It was found that a minority of the separated proteins exhibited some detectable change in relative rate of synthesis following axotomy. Actin exhibited a slight (less than 20%) increase in relative synthesis rate while tubulin did not change significantly. There were small but significant differences in the protein patterns following nerve crush, as opposed to nerve cut. Comparison of protein synthesis patterns from developing rat SCSG with those from intact and from axotomized adult SCSG failed to demonstrate any marked similarity between the developmental and the axotomy patterns.

Actins↗
PubMed1978

Test of some aging hypotheses using two-dimensional protein mapping.

We have compared the proteins from superior cervical sympathetic ganglia (SCSG) in young and old male Fischer rats. We have searched for the kinds of changes in protein size or charge which are predicted by such cellular aging theories as the error catastrophe theory, the somatic mutation theory, the cross-linkage theory, translational aging, the deamidation theory, and the autoimmune theory. SCSG from young (2 months to 1 year) and old (21-24 months) rats were labeled in vitro for 1 h with 14C-leucine prior to protein extraction for analysis. Protein analysis was on high-resolution, two dimensional polyacrylamide gels using O'Farrell's technique, with some modifications. Proteins were separated according to isoelectric point in one dimension and molecular weight in the second dimension. The changes predicted by the above aging theories were detected neither in the staining pattern, showing protein amounts, nor in the labeling pattern on autoradiographs of dried gels, showing newly synthesized proteins. The results suggest the possibility that, at least for rat, some other mechanisms for aging are present.

Aging↗
PubMed1976

Prevention of memory loss following puromycin treatment.

Female C57BL/6J mice were trained on a one trial passive avoidance response. Twenty-four hours later, they were treated with puromycin in combination with either 2.0 or 10.0 mg/kg of amphetamine, 0.3 mg/kg of strychnine, or 20.0 or 50.0 mg/kg of pentylenetetrazol. Tests one week after training revealed that treatment with these stimulant drugs prevented the memory loss characteristic of puromycin; an exception being those animals injected with the low dose of amphetamine. Biochemical determination of amino acid incorporation into protein revealed that none of the stimulant drugs used significantly altered the extent or the duration of protein synthesis inhibition induced by puromycin. These results are interpreted as showing that the amnesic effects of puromycin can be counteracted by a state of heightened nervous system excitation.

Animals↗
PubMedDate not supplied

Effects of alpha methyl-para-tyrosine on the recall of a passive avoidance response.

Treatment with alpha methyl-para-tyrosine 4 hr before training on a passive avoidance task altered recall in mice tested 24 hr after training. The observed alterations were dependent on the intensity of the footshock used during training. Retention of the avoidance habit was reduced by drug treatment when a footshock of 1.6 milliamperes (mA) was employed, while retention by drug-treated mice was enhanced when a footshock of 0.16 mA was used. No significant differences in retention were noted when a footshock of 0.8 mA or no footshock was employed. These results could not be explained on the basis of drug-induced changes in activity or sensitivity to footshock, of to state-dependent learning.

Animals↗
PubMedDate not supplied

A fragment of substance P with specific central activity: SP(1-7).

Amino-terminal fragments of substance P (SP), SP(1-7) and SP(1-8), were found to produce naloxone-reversible antinociception in the mouse similar to that produced by SP. Similar to SP, these peptides produce antinociception only within a narrow dose range. They have no activity on smooth muscle or blood pressure. These results suggest that contrary to peripheral effects of SP, which are mediated by receptors which recognize the carboxy-terminal part of the SP molecule, certain central actions of SP are mediated by receptors which recognize the amino-terminal part of the SP molecule. SP may be metabolized to this active fragment prior to its action at these receptors.

Analgesia↗
PubMedDate not supplied

Substance P and behavior: opposite effects of N-terminal and C-terminal fragments.

Most of the biological actions of substance P (SP) have been thought to be mediated by the carboxy-terminal portion of the peptide. Some of the behavioral effects produced by exogenous SP exhibit a strikingly different structure-activity relationship. The N-terminal heptapeptide fragment of SP, SP(1-7), inhibits nociceptive, aggressive and grooming behaviors and stimulates investigative motor behavior, but the C-terminal hexapeptide fragment analog pyroglutamyl-SP(7-11) exerts opposite effects. While the C-terminal fragment mimics the effects of administered intact SP on motor behaviors, the N-terminal fragment mimics the effects of intact SP on aggressive and nociceptive behaviors. The significant behavioral effects of SP(1-7) and the consistently opposite behavioral effects of N- and C-terminal fragments are important new findings.

Aggression↗
PubMedDate not supplied

Substance P and antinociception.

Substance P (SP)-induced antinociception is still a topic of controversy. Some investigators have failed to see an antinociceptive effect of SP, particularly following intraperitoneal administration. In the present experiments SP induced significant hot plate antinociception in male mice, following intraperitoneal administration. SP exhibited a bell-shaped dose response curve, and the antinociceptive effect was dependent on the pH of the vehicle. The antinociceptive effect of SP lasted for at least 1 hr and was naloxone-reversible. The antinociceptive effect of SP could be prevented by housing subjects collectively rather than individually during the experiment. In conclusion, the bell-shaped dose response curve, the solution pH and different testing procedures all influence the effects of SP on nociception. Given this complexity, it is not surprising that some experiments fail to demonstrate antinociception following SP administration.

Analgesics↗
PubMedDate not supplied

Modulation of isolation-induced fighting by N- and C-terminal analogs of substance P: evidence for multiple recognition sites.

Substance P (SP) significantly reduced fighting in mice made aggressive by prolonged isolation. The N-terminal heptapeptide fragment SP (1-7) also reduced fighting. The C-terminal fragment SP(4-11) was without activity, while the shorter C-terminal fragment analog less than E-SP(7-11) significantly increased isolation-induced fighting. The aggression-enhancing effect of less than E-SP(7-11) was antagonized by naloxone, which by itself had no significant effect. The aggression-reducing effect of SP(1-11) was significantly enhanced by naloxone, while the effect of SP(1-7) was unchanged. These results demonstrate that a behavioral effect of SP may be duplicated by an N-terminal fragment of the SP molecule, and that peptide fragments or analogs of the N- and C-terminal portions of the SP molecule can exert opposing effects on a specific behavior. These findings represent a structure/activity relationship that is strikingly different from any previously described for SP. The differing effects of naloxone on N- and C-terminal fragment analogs suggest that these two effects may be mediated by different mechanisms.

Aggression↗
PubMedDate not supplied

Age and strain differences in some behavioral effects of intracranial substance P.

Intracerebroventricular (ICV) injections of substance P (SP) induce a vigorous reciprocal hindlimb scratching (RHS) syndrome, accompanied by extensive grooming behavior. There is a significant (approximately 1000X) difference in responsiveness to SP, as measured by RHS and grooming, in mice as a function of genetic strain (Swiss/Webster, C57 or DBA) and age. There was considerable specificity in the ability of drugs to increase responsiveness in the least responsive type of mouse (aged DBA/2J). Responding in old DBAs was enhanced by high doses of naloxone, suggesting the involvement of opioid peptides. Significant enhancement of responding by alpha-methyl tyrosine and propranolol, but not by phenoxybenzamine or haloperidol, indicated that beta-adrenergic systems are also involved. Similar manipulations of serotonergic systems were without effect.

Age Factors↗
PubMedDate not supplied

The role of enzymatic processing in the biological actions of substance P.

There is considerable evidence that substance P (SP) is a neurotransmitter in the CNS. Current findings suggest that the effects of synaptically released SP are terminated by enzymatic breakdown, primarily by endopeptidase 3.4.24.11 (endo 24.11). The products of cleavage by endo 24.11 include the amino-terminal fragment SP(1-7). Evidence suggests that SP is involved in mediating baroreceptor reflex activity in the nucleus of the solitary tract (NTS). Microinjection of SP into the NTS lowered blood pressure and heart rate. Microinjection of SP(1-7) into the NTS reproduced the effects of SP on both heart rate and blood pressure. Intra-NTS injection of phosphoramidon, an inhibitor of endo 24.11 activity, completely blocked the effects of a subsequent injection of SP. This blocking effect of phosphoramidon was unaltered by pretreatment with the opiate inhibitor naloxone. In contrast, phosphoramidon failed to block the depressor and bradycardic effects of SP(1-7). The implications of these findings regarding the role of endo 24.11 in the metabolism of SP are discussed.

Animals↗