The interaction of chlordimeform, N'-demethylchlordimeform [N2-(4-chloro-o-toly1)-N'-methylformamidine], BTS-27271 (N'-methyl-N2-(2,4-xylyl)formamidine, the 2,4-xylyl analogue of N'-demethylformamidine], and amitraz with octopamine-, dopamine-, and 5-hydroxytryptamine-mediated enhancement of cyclic-AMP production was investigated in nerve cord homogenates of the American cockroach Peripfunetu umericuna. N'-Demethylchlordimeform, BTS-27271 and amitraz simulated the actions of the monoamines in enhancing cyclic-AMP production, whereas chlordimeform showed no such agonism. Additivity studies indicated that these formamidine derivatives were interacting with dopamine-and 5hydroxytryptamine-sensitive sites, in addition to their known interaction with octopamine-sensitive adenylate cyclase. N'-Demethylchlordimeform (Ki= 0 . 2~~) and amitraz ( K i = 0 . 5 p~) inhibited the dopamine-mediated response, but only N'-demethylchlordimeform ( K i = 2 p~) effected appreciable inhibition of the octopamine-response. Pharmacological characterisation of the formamidineinduced elevation of cyclic-AMP production indicated that the agonistic effects of formamidines are expressed primarily through the octopamine-sensitive adenylate cyclase, rather than the dopamine-or 5-hydroxytryptamine-sensitive sites. The results are discussed in the light of the proposal that the behavioural changes, associated with formamidine poisoning, reflect the cumulative effects of octopamine-agonism, and antagonism of the dopamine-and 5-hydroxytryptaminemediated processes.
During pseudopregnancy in the rabbit, plasma progesterone levels in the posterior vena cava fell rapidly from maximal concentrations of 9.8 +/- 0.7 (s.e.m.) ng/ml on Day 13 of pseudopregnancy to 2.0 +/- 0.6 ng/ml on Day 15. There was no significant increase in PGF levels at this time, although administration of indomethacin to a similar group of does delayed functional regression for over 7 days. Subcutaneous injection of 1 mg PGF-2alpha or 35 mg arachidonic acid on Day 9 of pseudopregnancy resulted in loss of luteal function as plasma progesterone levels fell significantly from about 6 to less than 1 ng/ml within 24 h. These findings indicate that the uterine factor responsible for luteolysis in the pseudopregnant rabbit may not be released in the form of PGF-2alpha.
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