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Biomedical subjects

D H Coy

Publications and source records attributed to D H Coy.

At least 19 recordsLinked to original sources
PubMed1979

Systemic administration of Met-enkephalin, (D-Ala2)-Met-enkephalin, beta-endorphin, and (D-Ala2)-beta-endorphin: effects on eating, drinking and activity measures in rats.

Rats were given four daily, interperitoneal injections (80 micrograms/kg) of Met-enkephalin, (D-Ala2)-Met-enkephalin-NH2, beta-endorphin, (D-Ala2)-beta-endorphin or the diluent (0.9% NaCl acidified to, 0.01 M with acetic acid). Animals were subsequently tested for food and water inake and activity. Met-enkephalin injections did not affect any of the measures but its (D-Ala2) analog reduced food intake and some of the activity measures in a complicated way. beta-Endorphin injections did not affect food or water intake; in familiar situations these animals were less active while novel situations seemed to potentiate activity. The (D-Ala2) analog reduced wheel running over 24 hours.

Animals↗
PubMed1979

Effects of an enkephalin analog on complex learning in the rhesus monkey.

Facilitation of the learning of a discrimination reversal task for a reward of food was found in rhesus monkeys after subcutaneous administration of a potent pentafluorinated enkephalin analog. (D-Ala2)-F5-Phe4-enkephalin-NH2. General activity, short-term memory, startle, and analgesia, however, were not significantly affected. In a within-subject design, each of 6 monkeys (3 males and 3 females) received each of 5 doses of the enkephalin analog (0.1, 1, 10, 100, and 1,000 microgram/kg). One daily injection was made for 7 consecutive days, including pre- and posttests on the first and last days with the diluent control. The enkephalin doses, with the exception of the 0.1 microgram/kg level, produced significantly faster learning than the diluent. Some sex differences were suggested by the data, but these effects are difficult to interpret. The results suggest that relatively small amounts of this analog given systematically can exert a reliable effect on a complex behavior such as reversal learning at doses devoid of opiate effects, due perhaps to enhanced cognitive flexibility rather than improvement in short-term memory or association formation.

Analgesia↗
PubMed1979

Possible non-narcotic component to action of opiate peptides on tonic immobility.

Chickens were tested in a tonic immobility paradigm after a single intraperitoneal injection of either 0.0, 0.1, 1.0, 10.0; 100.0, or 1000.0 microgram/kg of the potent opiate analog, (D-Ala2, F5Phe4)-Met-enkephalin-NH2. An inverted-U relationship was obtained, with 100 microgram/kg being the most effective in prolonging immobility. This dose was used in subsequent studies involving pretreatment with naloxone or diluent followed by treatment with diluent, (D-Ala2, F5Phe4)-Met-enkephalin-NH2 (a strong opiate), or (D-Phe4)-Met-enkephalin (a weak opiate). The results indicated that although naloxone had mixed effects in attenuating the duration of tonic immobility, even the analog with negligible opiate activity reliably potentiated the response. Therefore, a component of the effect of opiate peptides on tonic immobility could be due to a non-narcotic action.

Animals↗
PubMed1979

Analgesia after peripheral administration of enkephalin and endorphin analogues.

Several analogues of Met-enkephalin and beta-endorphin were tested for their analgesic properties after systemic injection. The latencies of mice to flick their tails away from a source of heat revealed that analogues of the opiate peptides can cause analgesia when injected by this route. In particular, compounds specifically designed to be more lipophilic or to possess additional binding sites were shown to be potent analgesic after peripheral administration.

Analgesics↗
PubMed1979

MIF-I's differential actions as an opiate antagonist.

The effects of MIF-I (Pro-Leu-Gly-NH2) were examined in three experimental conditions in which the opiate antagonist naloxone is active. MIF-I was found to block the analgesic effects of enkephalins and also morphine in the tail-flick test but not in the vas deferens assay. Unlike naloxone, MIF-I did not seem to reduce food intake in VMH-lesioned rats. The results suggest the possibility that MIF-I may represent a class of naturally occurring opiate antagonists with varying activities in independent situations.

Analgesics↗
PubMed1979

Experiments with a reported anorexigenic tripeptide: pyro-Glu-His-Gly-OH.

A newly described tripeptide, pyro-Glu-His-Gly-OH, which was reported to produce profound and long-term anorexia and weight loss in female mice, was initially tested in female rats. After total dose of either 8, 16, or 32 microgram SC of the peptide, administered across an eight day interval, there was no detectable effect on food intake, body weight, or estrous cycles of female rats. In a second study, we attempted to verify the anorexigenic potency of this peptide in mice. Total doses of 3.4 and 6.8 microgram, injected across a 20 day period, had no effect on the food intake or body weight of S/W albino female mice. Thus, the anorexigenic potency of pyro-Glu-His-Gly-OH has yet to be established.

Animals↗
PubMed1979

Endogenous opiates: through 1978.

The discovery of receptors in the brain for opiates and the structure of the endogenous peptides for these receptors has led to an explosion of interest in this field. The present review is the first of an annual series. It summarizes many of the highlights of research with opiate peptides published with a date of 1978 or earlier.

Animals↗
PubMed1979

Comparison of long-acting analogues of luteinizing hormone releasing hormone in man.

Currently, LHRH, when used therapeutically, is given by parenteral injection every 8 h. We have looked at the release of LH and FSH induced by five analogues of LHRH and compared this with gonadotrophin release after synthetic LHRH. The analogues were substituted in position 6 or in positions 6 and 10 and were given intravenously, intranasally or subcutaneously in three separate studies. After intravenous administration of 100 micrograms, all analogues caused greater release of LH and FSH than did synthetic LHRH. Given intranasally in a dose of 500 micrograms, three of the four analogues tested caused greater LH and FSH release than did LHRH. With tryptophan substitution in position 6 (D-TRP6-LHRH), mean LH levels in five subjects were still above the normal range 24 h after a single intranasal dose. The intranasal administration of selected analogues of LHRH has great potential in the treatment of conditions associated with deficient gonadotrophin secretion, provided that pituitary overstimulation, which may eventually lead to a decrease in LH and FSH output by the anterior pituitary, is avoided.

Administration, Intranasal↗
PubMed1979

Sensitive radioimmunoassay for somatostatin using N-[125I]-Tyr-somatostatin as labelled antigen.

A sensitive radioimmunoassay for somatostatin using N-[125I]-Tyr-somatostatin is described and compared with that using [125I]-Tyr1-somatostatin. The minimum detectable amount of somatostatin using N-[125I]-Tyr-somatostatin as tracer was 0.1 to 0.5 pg, which is approximately 10-fold lower than the lower detection limit of the RIA using [125I]-Tyr1-somatostatin. Moreover, it was found that the shelf-life of N[125I]Tyr-somatostatin was prolonged in comparison with labelled Tyr1-somatostatin. Human pancreatic and gastric extracts displayed immunological similarity to synthetic somatostatin tetradecapeptide.

Animals↗
PubMed1979

Minimal side-chain protection can be a successful strategy in solid-phase peptide synthesis.

The N-terminal tyrosine residue of Met-enkephalin could be readily incorporated without protection of its phenolic hydroxylgroup. Furthermore, the HF-cleaved product contained fewer impurities than that derived from hydroxyl-protected material. Despite the presence of Tyr in the center of the chain, an LH-RH antagonist, [D-Phe2, D-Trp3, D-Phe6]-LH-RH, could also be made in normal yield by incorporation of free Boc-Tyr. Syntheses of the same model peptide without protection of the Ser residue and protection of the Arg residue as the guanidine HCl salt also gave excellent yields of analog. Finally, the LH-RH inhibitor and a highly active agonist, [D-Leu6, desGly-NH2(10)]-LH-RH ethylamide, were synthesized without protection of Tyr, Ser and Arg, which enabled free peptides to be generated directly by ammonolysis and ethylaminolysis, respectively, without HF treatment. In all examples, no evidence emerged to suggest reaction of side-chains during synthesis.

Amino Acid Sequence↗
PubMed1979

Effect of D-Trp6-LH-RH on the pituitary-gonadal axis during the luteal phase in the baboon.

An effect of E-Trp6-LH-RH (superactive LH-RH agonist) in the pituitary and ovarian function was examined. Four regularly cycling baboons were used for this study. After determination of control values of plasma levels of LH, oestrogen and progesterone during the entire menstural cycle, D-Trp6-LH-RH was infused subcutaneously for 7 days during the early luteal phase in these four baboons. An infusion of D-Trp6-LH-RH increased plasma LH and oestrogen, but it failed to alter the plasma level of progesterone. From these results, it seems unlikely that 1) D-Trp6-LH-RH has a luteolytic effect, and 2) an increased ovarian oestrogen causes luteolysis in the baboon.

Animals↗
PubMed1979

Attempts to induce ovulation in amenorrheic patients using D-Ala-6-LH-RH propylamide.

Thirteen amenorrheic patients, two with primary amenorrhea, and eleven with secondary amenorrhea, including five with anorexia nervosa, were treated with an analog of LH-RH, D-Ala-6-desGly-10-LH-RH propylamide (D-Ala-6-LH-RH PA). The patients were follwed with checks of daily basal body temperature, cervical mucus characteristics, urinary total estrogens and pregnanediol, plasma LH and FSH, and twice-weekly clinical checkups. D-Ala-6-LH-RH PA was given continuously for 11 days at a dose of 50 microgram im from the 4th day of a steroid-induced cycle. Ethynyl estradiol (50 microgram orally) was given twice on day 14 followed by 250 microgram of D-Ala-6-LH-RH PA for the following 3 days. All the treated cycles were monophasic. Withdrawal bleeding occured in nine patients from the 4th to 6th days posttreatment. A significant total maximal increment in estrogens was found in seven patients, which was higher than the values obtained previously in the same patients with human menopausal gonadotropin. One patient conceived in the cycle immediately following discontinuation of treatment, indicating a possible effect of analog on the follicular development during the treatment; a normal baby was delivered. A second patient conceived three cycles afterwards, and two other patients began normal menstrual cycles.

Adult↗