The brain angiotensin (Ang) system plays an important role in the central control of vasopressin release. Using EC33, a selective aminopeptidase A inhibitor which blocks the metabolism of Ang II in Ang III, we previously reported that vasopressin release was under the control of Ang III and not Ang II. To determine accurately the action of EC33, the effects of intracerebroventricular injection of Ang peptides or EC33 on extracellular unit activity of vasopressinergic neurons in the supraoptic nucleus of urethane-anaesthetized rats were examined. Angiotensin II (15-30 ng) or Ang III (15 ng) increased the firing rate of all neurons tested. Conversely, EC33 (10 microg) reduced or completely abolished (30-60 microg) the basal firing rate for 4-6 min in all eight neurons tested. EC33 (30 microg) also inhibited the activity induced by 30 ng Ang II. It was concluded that the observed activity of Ang II required its conversion to Ang III and that endogenous Ang III may exert a tonic control on the basal firing level of vasopressinergic neurons.
SUMMARY1. Catecholamine secretion from cultured bovine adrenal chromaffin cells was decreased in a dose-dependent manner by the D2 dopamine agonists apomorphine and LY 17 1555.2. 45Ca2+ uptake was similarly inhibited and whole-cell Ca2+ currents were reduced by apomorphine.3. These inhibitory effects of D2 agonists depended on the secretagogue used, being much more pronounced for nicotine-evoked responses compared to high K+ stimulation, indicating another possible site of action of apomorphine up-stream of Ca2+ entry.4. Inhibition by apomorphine of nicotine-evoked responses could not be explained by competitive antagonism against nicotine or DMPP (1,1-dimethyl-4-phenylpiperazinium iodide).5. Apomorphine caused reductions of inward whole-cell nicotinic current evoked by ACh and nicotine.6. Inhibition of nicotine-evoked secretion and 22Na+ influx by apomorphine were not affected by tetrodotoxin, and voltage-dependent, whole-cell Na+ currents were unaltered by apomorphine.7. No evidence was obtained for increases in K+ conductance by apomorphine. 8. Action potentials recorded in whole-cell current clamp were blocked by apomorphine when they were triggered by nicotinic depolarization but not when they were elicited by direct electrical stimulation.9. Inclusion ofGDP-,-S in the pipette internal solution did not affect apomorphinedependent inhibition of nicotinic-evoked responses, while the decrease in whole-cell Ca2`current induced by apomorphine was completely inhibited in the presence of GDP-fl-S.
SUMMARY Immunocytochemical stains for laminin and type IV collagen can be used as markers for basement membrane and vascular endothelium. Thirty four follicular thyroid lesions were examined using these techniques to investigate two aspects: firstly, the relation between the extent of invasion and the integrity of basement membrane; secondly, whether the techniques could enhance the detection of tumour vascular invasion. The results showed that although basement membrane was lost in widely invasive tumours, preservation was seen in most but not all encapsulated tumours. The potential for improved recognition of vascular invasion was also found.Well differentiated follicular thyroid tumours continue to pose diagnostic problems. The distinction between adenoma and follicular carcinoma can rest on subtle histological changes. For the patient the designation of benign or malignant tumour can have major implications. Treatment may range from lobectomy and reassurance to total thyroidectomy, thyroxine replacement, and the administration of radioactive iodine. Such difficulties have prompted investigation of many other possible discriminating features.Recently, attention has been focused on the role of basement membrane in the development of invasion. Loss of basement membrane was shown in invasive tumours in many sites.' 2 In the thyroid recent immunofluorescence investigations showed that loss of basement membrane may be found in follicular thyroid tumours.34 To investigate the diagnostic potential of this in more detail we examined a larger series of these tumours, using antisera to laminin and type IV collagen, both of which are components of the basement membrane.56 The use of these techniques to enhance the detection of tumour vascular invasion was also shown recently.7 As vascular invasion by follicular thyroid tumours is considered to be of particular diagnostic importance, and present additional methods for enhancing the detection of vascular invasion are unhelpful, this aspect was also examined.Accepted for publication 1 July 1985 Material and methods Thirty four follicular thyroid tumours were obtained from the files of the Leicester Royal Infirmary and the Leicester General .Hospital. After examination of sections stained with haematoxylin and eosin these were subdivided by degree of invasion. Twenty one cases showed no evidence of invasion, four showed early invasion of capsule or capsular vessels, and nine widespread invasion. Examples of normal and hyperplastic thyroid were also included. IMMUNOSTAININGThe tissues were routinely fixed in 10% formol saline for up to 48 hours and processed in paraffin.After dewaxing 5 ,um sections were treated for two hours with 0 4% pepsin in 0-01N hydrochloric acid (pH 2.0) at 37°C. The sections were then blocked for endogenous peroxidase activity using hydrogen peroxide in methanol. Immunostaining was performed with the peroxidase-antiperoxidase technique using laminin antiserum (1:50 dilution) followed by counterstaining with haematoxylin. The method was derived fro...
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