Biomedical subjects

M Brownfield

Publications and source records attributed to M Brownfield.

5 recordsLinked to original sources

PubMed2001

Localization of 5-HT(7) receptors in rat brain by immunocytochemistry, in situ hybridization, and agonist stimulated cFos expression.

5-HT(7) receptors are recently identified members of the serotonin receptor family that have moderate to high affinity for several important psychotropic drugs. However, the lack of selective ligands has impeded the study of the brain distribution of these receptors. In this report, we describe the localization of 5-HT(7) receptor in rat forebrain by immunocytochemistry, in situ hybridization of 5-HT(7) mRNA, and functional stimulation of cFOS expression by 5-HT(7) receptor activation. The anatomical localization of 5-HT(7) mRNA in situ hybridization signal. Prominent immunostaining was apparent in numerous sites within the cerebral cortex, hippocampal formation, tenia tecta, thalamus and hypothalamus. 5-HT(7) receptors were detected in suprachiasmatic nucleus by both immunocytochemistry and in situ hybridization. At a microscopic level, both cell bodies and proximal fibers were strongly stained in these regions, suggesting a somatodendritic subcellular distribution. 5-HT(7) receptor-like immunoreactivity was further compared with 5-HT(7) mediated biological function by administering 8-OH-DPAT intracerebroventricular injection (icv)with WAY 100135 (to block 5-HT(1A) receptors) followed by double immunostaining localization of cFos activation and 5-HT(7) receptors. In all regions examined, cFos stimulation and 5-HT(7)-like immunoreactivity colocalized to the same neurons. Furthermore, cFos activation by 8-OH-DPAT was blocked by pimozide--a 5-HT(7) antagonist. Therefore, by using multiple strategies, we were able to localize 5-HT(7) receptors in rat brain unequivocally. The distribution of these receptors is consistent with their involvement in the control of circadian activity and the action of anti-depressants and atypical neuroleptics.

Animals↗

PubMed1997

Modulation of ventilatory control during exercise.

The control of ventilatory responses to mild or moderate dynamic exercise has been the subject of considerable debate for over a century. The prevailing view has been that the ventilatory response to exercise is stereotypical and rather unmalleable. However, paradigms involving novel associations of stimulus inputs have been shown to modulate breathing in short and longer time scales. The scope of this review includes examples of modified ventilatory responses to exercise which have been investigated in terms of neural mechanisms. An attempt to synthesise the available data into a model of neuromodulation is presented.

Animals↗

PubMed1997

Plasma renin activity and angiotensin I and aldosterone concentrations in cats with hypertension associated with chronic renal disease.

OBJECTIVE: To determine plasma renin activity (PRA), angiotensin I (Ang I), and aldosterone (ALDO) values in clinically normal cats and hypertensive cats with renal disease, and the relation of renin-angiotensin-aldosterone activation in response to treatment with beta-blockers or angiotensin-converting enzyme inhibitors. ANIMALS: 5 normotensive healthy control cats and 12 Untreated hypertensive cats with chronic renal disease. PROCEDURE: Untreated hypertensive cats received either propanolol (n = 6) or enalapril (n = 6) as initial antihypertensive treatment. PRA and baseline plasma Ang I and ALDO concentrations were measured prior to treatment. The difference in Ang I values at 2 hours (Ang I generated) and at time 0 (baseline Ang I) was divided by 2 to give the PRA value. Values for PRA, Ang I, and ALDO were obtained from 5 clinically normal, normotensive cats, and compared with those of hypertensive cats. RESULTS: Mean +/- SD PRA and baseline Ang I concentration were not significantly different between normotensive and hypertensive cats. Mean ALDO concentration was significantly (P = 0.0235) higher in hypertensive cats with renal disease (186.18 +/- 145.15 pg/ml), compared with that in normotensive controls (51.1 +/- 16.76 pg/ml). Eight hypertensive cats with ALDO concentration > 2 SD above the mean concentration in control cats had low (n = 3), normal (n = 4), or high (n = 1) PRA, suggesting variable activation of the renin-angiotensin-aldosterone axis in the hypertensive state. Overall, enalapril was effective long-term monotherapy in only 1 of 6 cats, and propranolol was ineffective as long-term monotherapy. CLINICAL RELEVANCE: Evaluation of the renin-angiotensin-aldosterone system in cats with hypertension associated with renal disease may lead to greater understanding of the pathophysiologic mechanisms of this disorder. In addition, identification of biochemical markers in hypertensive cats may permit selection of appropriate antihypertensive drugs. Propranolol and enalapril were ineffective antihypertensive agents in most cats of this study.

Adrenergic beta-Antagonists↗

PubMed1992

Pulsatile ACTH and cortisol in goats: effects of insulin-induced hypoglycemia and dexamethasone.

Insulin-induced hypoglycemia is a metabolic stress that stimulates secretion of adrenocorticotropic hormone (ACTH) and cortisol in a number of animal species. Dexamethasone is a potent synthetic glucocorticoid that suppresses the secretion of ACTH and cortisol. Both ACTH and cortisol exhibit complex secretory patterns demonstrating ultradian and circadian rhythms. This work investigated the pattern of ACTH and cortisol response to hypoglycemia in goats and the effect of dexamethasone on this response. Five goats were pretreated with dexamethasone (0.1 mg/kg) and 5 with saline. Blood samples were taken every 2 min for 60 min before and 60 min after administration of insulin (2.5 IU/kg, i.v.). Immunoreactive ACTH and cortisol were measured in all samples and glucose in selected samples. Data sets were analyzed for significant pulses with the Cluster Analysis program. Complete data sets were compared as well as those for each 30-min interval. Plasma glucose was lower than preinsulin levels at 10 min, declined rapidly between 10 and 30 min, and remained low 30-60 min after insulin injection in both treatment groups. Controls showed a rapid rise in ACTH and cortisol beginning 30 +/- 10 min postinsulin. The increase in mean plasma hormone levels during hypoglycemia was predominantly due to an increase in amplitude of secretory pulses for ACTH and cortisol compared with the 30 min before insulin. Dexamethasone significantly lowered mean ACTH and cortisol levels and prevented alteration in plasma ACTH and cortisol secretion during hypoglycemia but did not totally ablate pulsatile activity of either hormone. The amplitude of ACTH and cortisol pulses was significantly decreased by dexamethasone treatment. The frequency of cortisol but not ACTH pulses was also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1988

Immunohistochemical renin study of DES-induced renal tumor in the Syrian hamster.

Diethylstilbestrol (DES) treatment of a male Syrian hamster resulted in the development of a renal tumor and its widely scattered serosal metastases. Cells in both the primary tumor and metastatic nodules contained secretory granules. The tumors were transplanted serially into DES-supported and non-DES-supported host hamsters until DES-independent tumors developed. Rabbit antiserum to mouse salivary renin and rabbit antiserum to rat kidney resin were reacted with sections of the primary tumor, metastatic nodules, and all transport tumors. The sections were stained by the PAP and Vector-ABC-AP procedures. Renin-positive material was observed in all tumors. Plasma renin activity (PRA) was determined for the host hamsters carrying the renal tumor transplants and compared to the PRA values that had been determined for normal non-DES-treated male and female hamsters. It was found that the average PRA values of host hamsters carrying the tumor transplants were significantly higher than the normal PRA values.

Animals↗