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Apomorphine, a direct-acting dopamine agonist, stimulates release of growth hormone (hGH) and suppresses release of prolactin (PRL) from the anterior pituitary. Previous studies comparing the magnitude of these responses in schizophrenics and controls suggest that many acute (and some chronic) schizophrenics have exaggerated hGH responses; many chronic schizophrenics (and patients with tardive dyskinesia) have blunted hGH responses to apomorphine, and possibly blunted PRL responses. The present studies extend and confirm these findings in chronic schizophrenics; in addition, several studies were undertaken to further characterize these apomorphine-induced endocrine responses. Studies in which apomorphine was given on 2 or 3 separate occasions to each of five subjects indicate that the hGH response is a highly reproducible individual index, but PRL suppression is a less satisfactory measure. hGH responses to apomorphine were consistently antagonized by pretreatment with haloperidol, supporting the concept that the hGH-releasing effect of apomorphine is mediated by its action on dopamine receptors. Cyproheptadine pretreatment was associated with erratic increases or decreases in the hGH response to apomorphine, but did not alter PRL levels or apomorphine-induced PRL suppression. The relationship of these findings to biological hypotheses of schizophrenia and to neuroleptic-induced receptor changes is discussed. [ABSTRACT FROM AUTHOR]

Interactions with the microbiota influence many aspects of immunity, including immune cell development, differentiation, and function. Here, we examined the impact of the microbiota on CD8 + T cell memory. Antigen-activated CD8 + T cells transferred into germ-free mice failed to transition into long-lived memory cells and had transcriptional impairments in core genes associated with oxidative metabolism. The microbiota-derived short-chain fatty acid (SCFA) butyrate promoted cellular metabolism, enhanced memory potential of activated CD8 + T cells, and SCFAs were required for optimal recall responses upon antigen re-encounter. Mechanistic experiments revealed that butyrate uncoupled the tricarboxylic acid cycle from glycolytic input in CD8 + T cells, which allowed preferential fueling of oxidative phosphorylation through sustained glutamine utilization and fatty acid catabolism. Our findings reveal a role for the microbiota in promoting CD8 + T cell long-term survival as memory cells and suggest that microbial metabolites guide the metabolic rewiring of activated CD8 + T cells to enable this transition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study evaluated the relationship between two biochemical risk factors for coronary artery disease, serum lipids and dehydroepiandrosterone-sulfate (DHEA-S), and both fitness and perceived stress among a cohort of senior male Army officers (N = 331). The participants underwent a number of assessments gauging their fitness [exercise tolerance as measured by maximum ventilatory oxygen uptake (MVO2)], psychological well-being, and biochemical cardiovascular risk factors. Perceived stress was significantly and inversely related to DHEA-S levels, even after adjusting for age, though no relationship was found between perceived stress and serum lipids. Significant correlations were found between MVO2 and high-density lipoprotein cholesterol and inversely between MVO2 and triglycerides. Overall, the study's findings are generally consistent with the view that psychological stress and physical activity have opposite effects on parameters that affect cardiovascular status.

Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary artery disease (CAD). This study evaluated the effect of an SRP on metabolic and hormonal risk factors for CAD. Twenty army officers participating in an SRP, Group I, and a comparison group of seventeen SRP nonparticipants, Group C, volunteered to undergo measurement of dehydroepiandrosterone-sulfate (DHEA-S), cortisol, DHEA-S/cortisol ratio, testosterone, apolipoprotein-A1, apolipoprotein-B, triglycerides, cholesterol, fibrinogen, and leukocyte count both before and after the SRP period. No differences in the changes in biochemical risk factors for CAD were found between participant and nonparticipant except for DHEA-S. While Group C had a marked reduction in DHEA-S levels, Group I had a small increase. Previous studies indicate DHEA-S is inversely associated with extent of CAD and age-adjusted DHEA-S levels below 3.78 mumol/l confer an increased risk for CAD mortality. SRP participation appears to effect DHEA-S levels, possibly partially accounting for the benefits observed in SRPs among CAD patients.

Twenty army officers who participated in a stress/type A behavior reduction program and a comparison group of 17 officer nonparticipants volunteered to undergo a battery of psychological and behavioral tests before and after the program. Following the program, participants displayed a significantly greater reduction in average daily caloric intake and levels of perceived stress, anxiety, hostility, depression, psychological distress, and type A behavior as compared to the officers who did not participate in it. Given the fact that most of these psychological and behavioral factors have been found in previous studies to be related to an increased risk for coronary artery disease, it seems that the changes reported by the participants in the program are potentially healthful.

The development of selective irreversible ligands has proven to be an invaluable technique for the isolation, purification and characterization of many receptor proteins. An isothiocyanato-derivative of the muscarinic antagonist aprophen was synthesized and evaluated as a potential irreversible ligand for muscarinic receptors. This compound (aprophit) displaced [3H]N-methylscopolamine binding from rat cerebral cortex with a Ki of 3.1 x 10(-7) M. The inhibition was concentration-dependent and could not be reversed by extensive washing. Aprophit inhibited the acetylcholine-stimulated release of catecholamines from isolated, perfused guinea pig adrenal glands in a concentration-dependent manner. This inhibition was not reversed by perfusing the tissue with Locke's solution and was not due to a non-selective acylation by the isothiocyanate function. The data suggest that aprophit is selectively acylating muscarinic receptor proteins and thus may be useful in their further characterization.

The effects of the muscarinic antagonists, atropine, aprophen, azaprophen and pirenzepine, on catecholamine secretion stimulated by acetylcholine (ACh) and nicotine were studied using perfused and isolated guinea-pig adrenal glands. Sequential 2-min infusions of ACh (10(-5)M) at 15-min intervals evoked repetitive catecholamine secretory responses for at least 1 hr. This dose of ACh produced a predominantly muscarinic receptor-mediated catecholamine secretory response, which was inhibited by all muscarinic antagonists used. The order of potency was atropine greater than azaprophen greater than pirenzepine greater than aprophen, with IC50 values of 1.0 x 10(-9), 3.8 x 10(-9), 7.0 x 10(-8) and 1.3 x 10(-6) M, respectively. In comparison, repeated 1-min infusions of nicotine (2 x 10(-5) M) at 15-min intervals evoked progressively smaller catecholamine secretory responses over the course of 1 hr. At higher doses, atropine, azaprophen and aprophen also inhibited the nicotine-induced catecholamine secretion. In contrast, pirenzepine had no effect on the nicotinic response. The IC50 values for atropine, azaprophen and aprophen were 2.7 x 10(-6), 1.5 x 10(-6), and 3.2 x 10(-6) M, respectively. Because the antinicotinic effect of atropine and azaprophen was achieved at concentrations 2 to 3 orders of magnitude higher than those needed for the antimuscarinic effect, it was most likely not pharmacologically significant, but rather due to nonspecific inhibition of the nicotinic receptor.

We have previously reported that acute stress increases levels of rat pituitary cyclic AMP in vivo. The present study was conducted to test the hypothesis that stress-induced increases in pituitary cyclic AMP in vivo were mediated via CRF. We compared the effects of various stressors with the effects of CRF or epinephrine administration on pituitary cyclic AMP and plasma ACTH responses in vivo. Stressors, epinephrine or CRF increased levels of pituitary cyclic AMP. Pituitary cyclic AMP response to either immobilization or CRF was much greater at light onset than at lights off in rats maintained on a 12 hr light:12 hr dark lighting regimen. In rats with pituitary stalk transections, footshock did not increase levels of pituitary cyclic AMP, suggesting that some factor of central origin was required for this stress response. Exogenous CRF administration did increase levels of pituitary cyclic AMP in stalk-transected rats, while epinephrine increased levels in sham-operated but not in stalk-transected rats. Antisera to CRF markedly decreased pituitary cyclic AMP response to exogenous CRF administered 6 min following antisera and partially attenuated pituitary cyclic AMP response to forced running. Taken as a whole these data support a major role for CRF in the pituitary cyclic AMP response to stress.

We have previously reported that various stressors acutely elevate levels of pituitary cyclic AMP in vivo and that this stress response is not seen in animals tested 7 or 30 days post-adrenalectomy. In this report we present data that demonstrate that the loss of the pituitary cyclic AMP stress response following adrenalectomy is not the result of the loss of stress-induced adrenal epinephrine release. These data show that (1) although administration of epinephrine to intact rats does not elevate levels of pituitary cyclic AMP, administration of epinephrine to adrenalectomized animals does not elevate pituitary cyclic AMP levels in vivo; (2) splanchnic denervation prevents stress-induced adrenal epinephrine release but does not abolish stress-induced increases in pituitary cyclic AMP; and (3) the time course of the developing subsensitive pituitary cyclic AMP response to stress following adrenalectomy is much slower (2 to 3 days) than the loss of circulating epinephrine.

An overview of the biochemical events that occur when postsynaptic pineal beta-adrenergic receptors are stimulated is presented. Emphasis is placed on the importance of the adenylate cyclase system for the induction of N-acetyltransferase (NAT). Super- and subsensitive responses of NAT to receptor agonists are related to cAMP concentration, adenylate cyclase and phosphodiesterase activities and receptor binding sites.

Corticotropin releasing hormone (CRH) stimulation of ACTH release and cyclic AMP-mediated events involved in the control of ACTH release were compared in sham-operated and adrenalectomized rats. CRH-stimulated adenylate cyclase activity was decreased in pituitary homogenates from adrenalectomized animals. CRH-stimulated cyclic AMP accumulation was essentially abolished and CRH-stimulated cyclic AMP-dependent protein kinase (A-kinase) activity was decreased in freshly prepared anterior pituitary cells from adrenalectomized animals. Basal and CRH-stimulated ACTH release was elevated in these cells. Since ACTH release is increased in adrenalectomized rats despite the down regulation of CRH-linked pituitary mechanisms, we speculate that the site of action of disinhibition by corticosterone of ACTH release (or synthesis) following adrenalectomy is distal to the generation of cyclic AMP and/or that non-CRH mediated mechanisms assume a greater role in ACTH regulation following adrenalectomy.