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Biomedical subjects

R F Walker

Publications and source records attributed to R F Walker.

At least 73 records · Page 4Linked to original sources
PubMed1986

Mu/delta opioid site selectivity of some antidepressants.

Since pain and depression are influenced by opioids and antidepressants, it was of interest to explore their interaction with common CNS receptors. A method for binding site selectivity was used to evaluate antidepressant specificities in inhibiting mu versus delta opioid binding. With the very specific opioid probes used, DAGO and DPDPE, a wide range of antidepressant selectivities was found. These may represent different modes of interaction between mu and delta opioid sites and antidepressant compounds.

Animals↗
PubMed1985

Norepinephrine stimulates serotonin secretion from rat pineal glands, in vitro.

The purpose of this study was to determine if serotonin (5-HT) is secreted by the pineal gland and also to define the parameters of its secretion. After radiolabelling the endogenous 5-HT pool, individual pineal glands were placed within perifusion chambers and stimulated with norepinephrine (NE). [3H]5-HT was rapidly released within 1 min of stimulation and secretion continued throughout the period of exposure to NE. The findings suggest that 5-HT, in addition to melatonin, is a hormone of the pineal gland.

Animals↗
PubMed1985

Daily patterns of serotonin uptake in platelets from psychiatric patients and control volunteers.

Serotonin (5-HT) uptake into platelets from psychiatric patients and controls was measured in the morning and afternoon. Uptake varied with time of day in both groups studied, resulting in four recognizable patterns. Two patterns occurred in the majority of controls. In contrast, uptake patterns in the psychiatric patients were more variable, with each of the four patterns clearly represented. However, except for the fact that uptake was significantly decreased throughout the day in depressed patients, the patterns were not otherwise linked statistically to clinical condition. In any event, the greater variability of daily 5-HT uptake patterns in patients suggests that psychiatric disorders linked presumably to central nervous system (CNS) dysfunction are in some way reflected by labile platelet 5-HT pharmacokinetics.

Adolescent↗
PubMed1985

Neuroimmunomodulatory interactions of norepinephrine and serotonin.

Monoamine neuroleptics alter rodents responses to immunization, suggesting that norepinephrine (NE) and serotonin (5HT) are neuroimmunomodulatory in these animals. Although endocrine factors participate in their mechanism(s) of action, recent studies suggest that NE and 5HT also interact more directly with immunocompetent cells. This review provides an overview of evidence for a direct regulatory link between the nervous and immune systems and further speculates on the process by which NE and 5HT realize in part, their neuroimmunomodulatory potential. Anatomical data show that noradrenergic fibers of the sympathetic nervous system innervate lymphoid organs providing a channel of communication between neurons and lymphocytes. Presumably neural signals transmitted by NE are received by platelets that in turn, transduce them via 5HT into immunomodulatory messages. It is proposed that NE alters the capacity of platelets to sequester and/or catabolize 5HT, thus regulating its physiologically active pool in the plasma. Macrophages possess a 5HT uptake system, the kinetic properties of which make them sensitive to changes in plasma levels of the amine. Thus, through its ability to regulate plasma levels of 5HT, an immunosuppressive amine with access to macrophages, the nervous system can influence cells involved in antigen recognition. Support for this hypothetical immunomodulatory mechanism is gleaned from clinical and experimental studies. For example, individuals suffering emotional trauma are more susceptible than others to developing physical illness. It is of interest that platelet 5HT pharmacodynamics are often abnormal in patients with psychological disorders characterized by catecholamine deficits. Similar platelet changes have been achieved experimentally by treating rats with catecholamine antimetabolites. Additional support for the hypothesis derives from aging research since 'monoamine imbalance' and immune dysfunction are co-characteristics of senescence. In aging rodents and humans, central catecholamine deficits are associated with a decreased platelet affinity for 5HT and an increased plasma content of 5HT. Thus, emotional, spontaneous (age-related), or experimental changes in monoamine homeostasis have the potential to increase the risk of disease in affected individuals. Perhaps part of this effect results from endocrine perturbations associated with the trauma. However, a direct interaction between the nervous and immune systems involving monoamines is also possible, and a need for future study of this potentially significant mechanism for neuroimmunomodulation is indicated.

Aging↗
PubMed1985

Synergistic effects of estrogen and serotonin-receptor agonists on the development of pituitary tumors in aging rats.

The purpose of this study was to determine if pituitary 5-HT levels change as a function of age or endocrine state, and further if such changes are associated with pituitary pathology. Middle-aged constant estrous (CE) rats had larger (p less than 0.05) pituitary glands containing more (p less than 0.05) serotonin (5-HT) than those from young females or comparably aged, irregularly cycling rats. Ovariectomy lowered pituitary 5-HT content in middle aged CE rats. In contrast, pituitary weight and 5-HT content were increased in young rats of both sexes bearing subcutaneous, steroid-containing capsules that produced elevated levels of serum estradiol 17 beta. However, exogenous estrogen failed to raise pituitary 5-HT concentrations since pituitary weight increased more than 5-HT levels, even though the total amount of amine was significantly increased (p less than 0.05) compared with controls. These findings suggest that pituitary 5-HT increases during aging regardless of ovarian status and in addition, that total 5-HT content of the gland is increased further in hyperestrogenic states such as CE. Since pituitary adenomas occur more frequently in aged CE rats than in diestrous females or males, it was of interest to determine if 5-HT contributes to the tumorigenic effect of estrogen. Thus, the 5-HT receptor agonists zimelidine or quipazine were administered to ovariectomized rats bearing estrogen containing capsules. Rats treated with drugs had larger pituitaries containing more tumors than those receiving the steroid alone. However, these effects were dependent upon estrogen since pituitary pathology did not increase when ovariectomized rats were given 5-HT neuroleptics without the steroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Anticonvulsant therapy and cortisol elimination.

The effect of anticonvulsant therapy on early morning concentration of cortisol in saliva and plasma was assessed in a group of epileptic patients receiving regular phenytoin medication and the results compared with those obtained from a group of normal subjects not receiving drug therapy. Values of cortisol in matched samples of plasma (331 +/- 23 nmol l-1, mean +/- s.e. mean, n = 6) and saliva (11.4 +/- 0.9 nmol l-1, mean +/- s.e. mean, n = 9) provided by epileptics did not differ significantly from those in the plasma (334 +/- 41 nmol l-1, mean +/- s.e. mean) and saliva (12.0 +/- 2.0 nmol-1, mean +/- s.e. mean) of healthy volunteers (n = 12). Six anticonvulsant-treated epileptics, together with six age and sex matched normal volunteers, each received intravenous dexamethasone (1 mg h-1) to determine the half-life of cortisol in plasma and saliva. In the anticonvulsant-treated group, the half-life of cortisol in plasma (73 +/- 5 min, mean +/- s.e. mean) and saliva (83 +/- 5 min, mean +/- s.e. mean) was reduced significantly (P less than 0.01 plasma, P less than 0.05 saliva) from that observed in healthy volunteers. In patients, the half life of cortisol and antipyrine showed a significant correlation (r2 = 0.75, P less than 0.05 plasma, r2 = 0.71, P less than 0.05 saliva). The antipyrine half-life in saliva was reduced significantly (P less than 0.02) and the antipyrine clearance rate, increased significantly (P less than 0.005) in the treated epileptic group, reflecting drug-induced microsomal enzyme production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Characterization of profiles of salivary progesterone concentrations during the luteal phase of fertile and subfertile women.

Salivary progesterone concentrations were measured in daily samples collected between 08.00 and 09.00 h throughout the menstrual cycle of women with a history of fertility. The luteal-phase salivary progesterone profiles in these normally menstruating, healthy women were characterized using a computer program based on a cumulative sum procedure. This method of statistical analysis led to the development of a 'progesterone boundary diagram', the inner and outer domains of which distinguished between the profiles of salivary progesterone considered compatible with fertility, and those observed in subfertile women attending an infertility clinic.

Adolescent↗
PubMed1985

The use of salivary steroids to monitor circadian rhythmicity on expeditions in the arctic.

The circadian variation in salivary cortisol concentration was investigated in four men during a traverse on foot, of the Greenland ice cap and of salivary cortisol and testosterone on a summer expedition to Spitzbergen. In both instances circadian rhythmicity was demonstrated both before leaving the U.K. and throughout the expedition. The acrophase of the rhythms followed the changes in activity patterns on both expeditions although there was a dissociation between the cortisol and testosterone following an acute 8 hr phase shift in Spitzbergen. The mesor of cortisol in both instances tended to be higher than in the U.K. but the difference was never statistically significant. This work demonstrates the feasibility of using salivary steroid concentrations to investigate their circadian rhythmicity in circumstances where frequent blood sampling would be precluded.

Adult↗
PubMed1985

Influence of serotonin on the immune response.

The present study investigates the influence of pharmacological agents known to regulate biosynthesis of the neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) on the primary antibody response to sheep red blood cells (SRBC) in the CBA mouse. Systemic administration of 5-HT (4-100 mg/kg) or its precursor, 5-hydroxytryptophan (5-HTP, 50-400 mg/kg), 30-60 min before immunization resulted in dose-dependent suppression of both the IgM and IgG plaque-forming cell (PFC) response to SRBC. Conversely, para-chlorophenylalanine (PCPA, 250 mg/kg), which inhibits the rate-limiting enzyme (tryptophan hydroxylase) in 5-HT biosynthesis, markedly enhanced IgM and IgG antibody production when injected 48 hr prior to antigen. Effects of these drugs on immune processes appeared independent of observed changes in plasma corticosterone levels. Further, immune function was preserved following selective depletion of brain serotonin through intracisternal injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) in mice pretreated with desmethylimipramine (DMI). Thus, immunomodulation by serotonin appears to be mediated via peripheral mechanism(s).

5,7-Dihydroxytryptamine↗
PubMed1984

Impact of age-related changes in serotonin and norepinephrine metabolism on reproductive function in female rats: an analytical review.

This review attempts to reconcile changes in brain NE and 5HT metabolism with the effects of aging, drug treatment and altered photoperiods on phasic and tonic release of LH in the female. A hypothesis is presented in which 5HT has "indirect" and "direct" effects on LH surges. The "indirect" ones facilitate LH surges via a generalized effect of 5HT on temporal organization within multiple neuroendocrine axes. Thus, 5HT promotes circadian rhythmicity in many systems due to its participation in the biological "clock" mechanism of the hypothalamus. The "direct" ones that are specific to the LH releasing mechanism also occur for 5HT (inhibitory) as well as for NE (facilitory) due to the interaction of these transmitters with LH-RH secreting neurons. It is proposed that metabolic changes during aging that favor 5HT at the expense of NE obliterate the facilitatory effects of both amines while enhancing the inhibitory component of 5HT's influence on LH secretion.

Aging↗
PubMed1984

'Maternity blues' and hormone levels in saliva.

Psychological symptoms were monitored for 5 days post partum, and specimens of saliva were taken for assays of cortisol, progesterone and oestradiol. Of 40 normal primiparous mothers, the 5 who experienced most severe 'maternity blues' were matched with 5 who were symptom-free. On the day of symptoms, concentrations of progesterone and oestradiol were significantly higher in the experimental group (P less than 0.02 and less than 0.05, respectively), but mean cortisol concentrations did not differ between the groups. This pilot study has demonstrated the potential value of using a non-invasive technique (obtaining specimens of saliva) in conjunction with determinations of a predictable mood change.

Depression↗
PubMed1984

Quantitative relationship between light intensity and luteinizing hormone surges in ovariectomized rats treated with estrogen.

The purpose of this study was to determine if patterns of gonadotropin secretion during estrogen-induced luteinizing hormone (LH) surges are altered by abrupt changes in light exposure. When light intensity was increased approximately threefold, before the "critical period" or during the rising phase of the LH surge, serum LH increased significantly (P less than 0.01) compared to control values. Furthermore, LH surges were prolonged when exposure to light of high intensity was continued beyond the normal extent of the photophase. In contrast to the effects of increased light intensity, acute darkness did not alter the magnitude of LH surges compared with controls exposed to light of low intensity. Thus, phasic LH secretion is enhanced by abrupt increases in light intensity, and the duration of LH secretion can be extended by prolonging the photophase. Although LH surges occur in total darkness, this study suggests that light modulates the intensity of the signal for LH secretion by a stimulatory action.

Animals↗
PubMed1984

Salivary cortisol levels in true and apparent hypercortisolism.

Total plasma cortisol measurements may be misleading when there are variations in the plasma cortisol-binding protein capacity resulting from drugs, pregnancy or congenital alterations in cortisol-binding globulin (CBG). Salivary cortisol levels, which represent the free component of plasma cortisol, are less affected by alterations in protein binding and have been used in the investigation of hypothalamic-pituitary-adrenal disorders. This study compares these two indices of adrenal function in conditions of true hypercortisolism and spurious hypercortisolism (resulting from oral contraceptive medication or pregnancy). The circadian variation of cortisol in plasma and saliva was studied in six patients with unequivocal hypercortisolism and compared with normal volunteers. In the normal group, plasma and salivary cortisol levels taken at 0900 h were significantly higher than those taken at 2400 h. Patients with Cushing's syndrome failed to show a significant difference between plasma and salivary cortisol levels collected at 0900 and 2400 h. Five patients with pituitary-dependent Cushing's disease, one patient with an adrenal carcinoma causing Cushing's syndrome and seven normal subjects each received a dexamethasone suppression test using a continuous infusion of dexamethasone sodium phosphate at a rate of 1 mg/h. There was no significant difference in the half-life disappearance rate of endogenous cortisol in either plasma or saliva comparing grouped data from patients with pituitary-dependent Cushing's disease with that of normal subjects. Failure of suppression of both plasma and salivary cortisol levels was observed in the one patient with adrenal carcinoma during dexamethasone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗