Biomedical subjects

M I Phillips

Publications and source records attributed to M I Phillips.

201 records · Page 12Linked to original sources

PubMedDate not supplied

Characterization of the synthesis and release of dopamine in LLC-PK1 cells.

The ability of a renal epithelial cell line of porcine origin (LLC-PK1) to synthesize dopamine (DA) from L-dopa and release DA into the culture media was studied. L-Dopa was rapidly taken up by LLC-PK1 cells and converted to DA which was then released into the media. L-Dopa uptake and conversion to DA was competitively inhibited by other aromatic amino acids (Tyr and Phe). Studies were conducted to assess L-dopa uptake, DA synthesis and DA release in LLC-PK1 cells in response to changes in the ionic composition of the Krebs-Ringer bicarbonate (KRB) buffer media and to various drugs known to alter renal transport function. Sodium chloride addition to KRB media resulted in enhanced DNA release into the media that was significantly attenuated by both quinine (1 mM) and benzamil (0.1 mM). Other sodium salts (sodium acetate and sodium phosphate) also enhanced DA release from LLC-PK1 cells. Salts containing chloride (LiCl, NH4Cl, choline chloride) stimulated a greater efflux of DA from LLC-PK1 cells than sodium salts at equimolar concentrations. Osmotic stimuli (sucrose, mannitol and dextran, 50-200 mM) also elicited increased DA release from LLC-PK1 cells into the media but not to the same extent as inorganic salts. DA release (secretion) from LLC-PK1 cells was strongly inhibited (25-50%) by drugs known to be substrates for the renal cation transport system. These studies have characterized extensively the factors that govern and regulate the synthesis of DA from L-dopa and the transport system responsible for the secretion (release) of intracellular DA into the media.

Animals↗

PubMedDate not supplied

Angiotensin-like immunoreactivity in the brain of the spontaneously hypertensive rat.

Evidence for the brain renin-angiotensin system being involved in the hypertension of the spontaneously hypertensive rat (SHR) includes central administration of angiotensin II (AII) antagonists and converting enzyme inhibitors that lower blood pressure in SHR. Using the unlabeled antibody enzyme method, we have found a significant difference in the distribution of brain angiotensin in SHR and Wistar-Kyoto controls (WKY). Six rats of each group were perfused with buffered picric acid-paraformaldehyde, and their brains sectioned at 50 and 100 mu. The sections were reacted with a 1:1000 dilution of AII antiserum for 36 hours followed by goat antirabbit immunoglobulin G and rabbit peroxidase antiperoxidase. For controls, preabsorption with AII, arginine vasopressin or preimmune serum were evaluated. The results showed over twice as many cells and fibers staining for AII-like immunoreactivity in SHR. The AII immunoreactive cell bodies were localized, in the order of their relative preponderance, in supraoptic and paraventricular nuclei of the hypothalamus, hippocampus, and cortex. The most prominent demonstration of AII-like immunoreactivity was observed in fiber profiles containing densely stained varicosities, which were present in many neuroanatomical subdivisions of the brain and brain stem including anterior and middle hypothalamus, basal ganglia, thalamus, locus coeruleus, nucleus of the solitary tract, limbic structures, and reticular formation. The increased fiber staining in the SHR was particularly evident in the frontal hypothalamic region, medial preoptic, and stria terminalis. We conclude that the results support the hypothesis of brain AII involvement in hypertension.

Angiotensin II↗

PubMedDate not supplied

Central pressor action of neurotensin in conscious rats.

The effects of neurotensin upon blood pressure in conscious rats were examined after intracerebroventricular (i.v.t.) or intravenous (i.v.) administration of this peptide. Whereas i.v. injected neurotensin (0.1-2.0 microgram/kg) was depressor, i.v.t. injected neurotensin (1 microgram and above) was pressor. Peripheral depressor responses could not be repeated in the same animal due to tachyphylaxis, but central pressor responses were repeatable without reduction in magnitude, showing that the two effects were separate entities. Thyrotropin-releasing hormone (TRH), which is reported to be a potent neurotensin antagonist, completely abolished the neurotensin depressor response, and attenuated the central pressor action. TRH did not alter the central pressor effect of another peptide, angiotensin II (AII). The potent AII receptor antagonist saralasin, while abolishing the central pressor effect of AII, was completely without effect upon the neurotensin-induced pressor response. These results indicate that i.v.t. injected neurotensin and AII stimulate a rise in blood pressure via different receptors. The alpha-adrenergic antagonists phentolamine, prazosin, or yohimbine (injected i.v.t.) involvement of the sympathetic nervous system in this response. These results are discussed in relation to the central pressor actions of other neuropeptides.

Animals↗