Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance.

Doxorubicin (DOX), an anthracycline, is broadly considered the most active single agent available for treating breast cancer but has been known to induce cardiotoxicity. Although DOX is highly effective in treating triple-negative breast cancer (TNBC), DOX can have poor outcomes owing to induction of chemoresistance. There is an urgent need to develop new therapies for TNBC aimed at improving DOX outcome and DOX-induced cardiotoxicity.

Substance P causes seizures in neurocysticercosis.

Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes.

Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro.

The atypical antipsychotic olanzapine has relatively high affinity for a number of neuronal receptors in radioreceptor binding assays. The ability of olanzapine to activate or antagonize a number of neuronal receptors was investigated in vitro, in cell lines transfected selectively with receptor subtypes and in receptor-selective isolated tissue studies. Olanzapine had no agonist activity at any of the receptors examined.

Muscarinic agonist inhibition of rat striatal adenylate cyclase is enhanced by dopamine stimulation.

Rat striatal adenylate cyclase stimulated with combinations of 100 microM dopamine plus 40-100 nM forskolin was inhibited to a significantly greater extent by the muscarinic agonist carbachol than was forskolin-stimulated activity in the absence of dopamine. In the presence of Ro 201724 as phosphodiesterase inhibitor, a 100 microM concentration of the adenosine agonist 2-chloroadenosine stimulated adenylate cyclase activity 6.6 -fold over basal activity.

Forskolin stimulation of cyclic AMP accumulation in rat brain cortex slices is markedly enhanced by endogenous adenosine.

Stimulation of cyclic AMP (cAMP) accumulation in rat cortex slices by 1 microM forskolin (F) was markedly reduced (96%) by treatment with adenosine deaminase (ADA). The effect of ADA was progressively less at higher concentrations of F, but still inhibited the response by 50% at 100 microM F. ADA-mediated inhibition of the cAMP response to 1 microM F was completely reversed by 5 microM 2-chloroadenosine (CA), an ADA-resistant analogue.

Serotonergic changes following proestrous treatment with p,p'-DDT.

The effects of 25 and 75 mg/kg p,p'-DDT on the CNS serotonergic system were examined in proestrous female rats. Females were treated with p,p'-DDT on the morning of proestrus and were sacrificed that evening. Levels of serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in cortex, hippocampus, hypothalamus and preoptic areas.

Effects of chlordecone on progesterone receptors in immature and adult rats.

The ability of the chlorinated pesticide chlordecone to induce the CNS (hypothalamus and preoptic area) plus pituitary and uterine progesterone receptors was examined in CDF-344 female rats following treatment with 25 micrograms estradiol or with 75 mg/kg chlordecone. In adult ovariectomized rats and in intact immature rats, estradiol increased progesterone receptors in neural and uterine tissues. This was in contrast to the effect of chlordecone.

Estradiol and chlordecone interactions with the estradiol receptor.

The in vivo and in vitro effects of the chlorinated pesticide, chlordecone, on the estradiol receptor of adult ovariectomized CDF-344 rats were examined. Chlordecone's competition with [3H]estradiol for binding to the estradiol receptor in vitro was similar whether receptors were derived from neural or uterine tissue. In vivo, chlordecone led to nuclear retention of estradiol receptors in both tissues, but in comparison to estradiol, the latency for such retention was slower following chlordecone.

Proestrous effects of chlordecone on the serotonin system.

This study concentrates on the role of the serotonin system in mediating the proestrous effects of chlordecone on female rodent sexual behavior. The pesticide was examined within the context of serotonin changes taking place on proestrous. Between morning and evening on the day of proestrus there was an increase in 3H-5-HT binding, an increase in serotonin (5-HT) and an increase in 5-hydroxyindoleacetic acid (5-HIAA).

Variations in binding of [3H]5-HT to cortical membranes during the female rat estrous cycle.

The binding of [3H]5-hydroxytryptamine ([3H]5-HT) to cortical membranes was examined in female rats during diestrus, proestrus and estrus. Serotonin binding was lowest during the early afternoon of proestrus and highest during the afternoon of estrus with diestrous values in between. The high estrous values were associated with a significant increase in Bmax and a decrease in Kd.

Serotonin receptors in striatum after chlordecone treatment of adult female rats.

Serotonin receptors were examined in various brain regions of female rats 24 hours after treatment with 25, 50 or 75 mg/kg chlordecone. With each dose of chlordecone, there was a significant reduction in the specific binding of 3H-5-HT to striatum. Binding to cortex, hippocampus, hypothalamus, midbrain or brainstem did not systematically vary as a function of treatment conditions.

Failure of chlordecone (Kepone) to induce behavioral estrus in adult ovariectomized rats.

The effect of chlordecone on behavioral estrus was examined in adult ovariectomized female rats. Chlordecone has been reported to resemble estrogen in altering pituitary secretions, in producing vaginal cornification, in increasing uterine weight and in competing for binding to the estrogen receptor. In the present study, 10, 25, 50 or 75 mg/kg chlordecone was substituted for estrogen in the estrogen-progesterone priming sequence used to facilitate sexual behavior of ovariectomized female rats.