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At least 379 records · Page 21Linked to original sources
PubMed1993

Identification of octopaminergic agonists with selectivity for octopamine receptor subtypes.

Previous studies utilizing relatively nonselective octopamine (OA) agonists have suggested that differences may exist between the pharmacological responses of Gs-linked OA receptors found in various insect tissues and species. The present experiments identify and characterize two structurally related phenyl(imino)imidazolidine (PII) derivatives that demonstrate a significant degree of OA receptor subtype selectivity and, when used in concert, are able to distinguish tissue- and/or species-related differences in OA receptor response. In membrane preparations, 2,4,6-triethyl-PII (TEP) showed > 60-fold selectivity for activating adenylate cyclase in the firefly light organ vs. that in Manduca sexta nerve cord, whereas 2,4,6-trimethyl-PII (TMP) showed > 2-fold selectivity for activating adenylate cyclase in Manduca nerve cord vs. that in the light organ. Within the same tissue, the potency ratio for TEP/TMP was 29 in the light organ and 0.2 in the nerve cord, a degree of selectivity much greater than that of other PII analogs examined. Corresponding physiological measurements of octopaminergic response correlated well with biochemical measurements. TEP was 24-fold more potent than TMP for OA-mediated light emission in intact firefly light organs, whereas TMP was more than 3-fold more potent than TEP as an antifeeding agent in Manduca. These results indicate that the PII analogs, TEP and TMP, should prove quite useful for characterizing and differentiating OA receptor subtypes in various tissues and species. In addition, these findings provide further evidence that light emission in fireflies and disruption of feeding in Manduca involve Gs-linked OA receptors, subtypes of which are distributed differently in the end organs of these two species.

Adenylyl Cyclases↗
PubMed1985

Effects of debrisoquin on the excretion of catecholamine and octopamine metabolites in the rat and guinea pig.

The effects of debrisoquin, administered daily for 4 days to rats (40 mg/kg, i.p.) and guinea pigs (4 mg/kg, i.p.), were determined for urinary excretion of several acidic and neutral amine metabolites, including the norepinephrine metabolites, 3-methoxy-4-hydroxyphenethylene glycol (MHPG) and vanillylmandelic acid (VMA), the dopamine metabolites, 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), and homovanillic acid (HVA), and the octopamine metabolite, p-hydroxyphenylglycol (pHPG). The excretion of MHPG was reduced to 32% of control in rats and to 46% in guinea pigs, HVA was reduced to 64 and 80% in these two species, respectively, and MHPE was lowered to 59% of control in the rat but was not affected in the guinea pig. DHPE and pHPG were not altered significantly in either species. VMA was a minor metabolite in both species, being less than 6% of MHPG, and its formation was blocked only partially (rat) or not at all (guinea pig) by debrisoquin. The data refute the idea based on previous in vitro studies that VMA is a major metabolite of norepinephrine in the periphery of the guinea pig as it is in man.

3-Methoxy-4-hydroxyphenylethanol↗
PubMed1999

Titres of biogenic amines and ecdysteroids: effect of octopamine on the production of ecdysteroids in the silkworm Bombyx mori.

At day two, a sharp peak of octopamine (OA) was observed in last instar female Bombyx mori larvae. This peak also appeared in male larvae a day later than in females at day three. An OA peak was also observed before the 3rd ecdysis. However, no OA peaks were observed in 4th instar larvae. At day eight and nine of the 5th instar, another OA peak was observed for male and female, respectively. A peak of tyramine (TA) was found at day one followed by a peak of OA at day two in 3rd instar larvae. At day two, a day before OA peak, a peak of TA was observed for male insects and before the 2nd peak of OA, TA titre was also high in 5th instar larvae. Immediately after 3rd ecdysis, a high titre of DL-beta-(3,4-dihydroxyphenyl)alanine (DOPA) was observed, followed by a peak of dopamine (DA) at day five. A peak of DOPA was found at day one followed by a peak of DA at day two in 3rd instar larvae. Similarly, a small peak of DOPA was observed at day two, followed by an increase of DA at days eight and nine after the 4th ecdysis. Ecdysteroid peaks were observed just before the 3rd and 4th ecdysis and an ecdysteroid titre increased after the start of spinning. The effects of OA and JH on production of ecdysteroids by prothoracic glands (PGs) were examined in order to identify neuromediators responsible for triggering pupation in B. mori larvae. Exogeneous OA (10-100 mM) reduced and 10 &mgr;M OA stimulated the production of ecdysteroids in the presence and absence of brain extracts by PGs in the final instar (day five) of B. mori in vitro. Meanwhile, exogeneous JHI (10 &mgr;g/ml) stimulated and at 5 &mgr;g/ml it reduced production of ecdysteroids in the presence of brain extracts. Gramine, an OA antagonist, delayed pupation when applied in the diet. Thus, OA may produce some biological effects on the programming of larval-pupal development.

Journal Article↗
PubMed1999

Three-dimensional pharmacophore hypotheses for the locust neuronal octopamine receptor (OAR3). Part 2: agonists.

Three-dimensional pharmacophore hypotheses were built from a set of 43 agonists against octopamine receptor class 3 (OAR3) in locust nervous tissue. Among the 10 chemical-featured models generated by program Catalyst/Hypo, a hypothesis including hydrogen-bond acceptor (HBA), hydrophobic (Hp), and hydrophobic aliphatic (HpA1) features was considered to be important and predictive in evaluating OAR3 agonists. While the ideal and null hypotheses had a cost of 156.40 and 239.20, respectively, the 10 resulting hypotheses possessed costs from 169.89 to 175.81. The best hypothesis that was confirmed to have a 95% chance of true correlation yielded a low RMS of 0.757 and high regression r of 0.933. Active agonists mapped well onto all the features of the hypothesis such as HBA, Hp, and HpA1. On the other hand, inactive compounds were shown to be difficult to achieve the energetically favorable conformation which is found in the active molecules in order to fit the 3-D chemical feature pharmacophore models.

Animals↗