Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

Summary The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were supporessed with sublethal to acutely lethal dosages (20, 30 and 40 g/kg, s.c.) during the acute excitatory phase of intoxication and at 6–8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 g/kg soman whereas there was a protracted increase with 30 g/kg. Corticosterone was not significantly elevated with 40 g/kg, but death occurred at 13±4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.Supported by US Army Medical Research and Development Command Contract DAMD 17-81-C-1202.     

Differential effects of prostaglandins and isoproterenol on cAMP content and Na,K pump activity in rat submandibular acini

Summary The -adrenergic agonist isoproterenol and prostaglandins E₁ and E₂ (but not F₂) increased the cAMP content of rat submandibular acini in vitro, but only isoproterenol enhanced ouabain-sensitive⁸⁶Rb (K) uptake. These findings suggest that cAMP is not involved in the activation of the Na, K pump in salivary cells.     

An enzyme immunoassay for mouse epidermal growth factor utilizing a liquid phase double-antibody system

Summary An enzyme immunoassay for mouse epidermal growth factor (EGF) involving a liquid phase double-antibody system was developed. The EGF--galactosidase conjugate prepared was stable for at least 8 months. By this method, EGF was detectable at a concentration as low as 20 pg per tube. The concentrations of EGF in various tissues of mice are also presented.This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.     

A major metabolite of Δ1-tetrahydrocannabinol reduces its cataleptic effect in mice

Summary The results described here demonstrate that THC-induced catalepsy in mice can be substantially inhibited by the prior administration of ¹-THC-7-oic acid, the major metabolite of THC in most species including humans. This raises the possibility that the intensity and duration of action of THC may depend to a large degree on the levels of this metabolite at the sites of action.We thank the National Institute on Drug Abuse for supporting this project by grants DA-02043 and DA-02052 and for supplying all of the cannabinoids. One of us (S.B.) is also the recipient of a Research Scientist Award from NIDA. We are grateful to Kristen Carlson and Thomas Honeyman for helpful suggestions in preparing this report.     

Pharmacological versus binding analysis of receptor systems: How do they interplay? Myometrial cell receptors for oxytocin as a paradigm

Summary Binding studies in various biological systems frequently indicate the presence of several binding sites for a biologically active ligand. They differ in their affinity for the ligand in question, binding capacity, and Hill coefficient, which suggests differences in the mechanisms of the binding site-ligand interactions. Identification of the true receptors (sites initiating a cellular response) appears to be difficult. Three clusters of binding sites for oxytocin were found on rat myometrial cells. The oxytocin receptor seems to be linked to the medium-affinity site; the cooperation between the high-and medium-affinity sites in eliciting the uterotonic response seems likely, but lacks experimental proof. Dose-response analysis in partially irreversibly inhibited uterus preparations, the method of equipotent doses (Furchgott-Bursztyn method), and structure-activity analysis of oxytocin-like peptides acting as competitive inhibitors of oxytocin, turned out to be suitable for pharmacological analysis of this receptor system.     

Tamoxifen ‘sex reverses’ alligator embryos at male producing temperature,but is an antiestrogen in female hatchlings

Summary Tamoxifen is an anticancer drug widely used in the treatment of estrogen-dependent breast cancer. In hatchling alligators it acts as a pure antiestrogen in that it completely blocks the effect of estradiol-induced oviductal hypertrophy and completely blocks the estradiol-induced hepatic vitellogenin secretion. Paradoxically, when injected into alligator eggs incubated at 33°C, a temperature which would normally result in 100% male hatchlings, tamoxifen sex reverses the embryos into apparently normal female hatchlings.     

Metabolism of 3β-hydroxycholest-5-en-26-oic acid in hamsters

Summary Metabolism of 26-hydroxycholesterol to 3-hydroxychol-5-en-24-oic acid and other C24-bile acids has been expected to occur by way of 3-hydroxycholest-5-en-26-oic acid in studies in vitro. 3-Hydroxycholest-5-en-26-oic acid was infused intravenously into bile fistula hamsters and the following C24-bile acids were identified: 3-hydroxychol-5-en-24-oic acid, lithocholic acid, chenodeoxycholic acid, and a small amount of cholic acid.