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Biomedical subjects

E I Bloomquist

Publications and source records attributed to E I Bloomquist.

13 recordsLinked to original sources

Expression of substance P and its precursor forms in vagal, tracheal, and lung tissues of the guinea pig.

Steady-state levels of the prototypic tachykinin neuropeptide substance P (SP) and its major precursor form substance P-glycine (SP-G) were detected and authenticated in guinea pig vagal and respiratory tissues by radioimmunoassay (RIA), combined high-performance liquid chromatography (HPLC)/RIA analyses, and immunohistochemistry. Four antisera were employed: anti-SP that recognizes the amidated COOH-terminal of SP and is specific for the mature peptide, anti-SP4-10 that recognizes the midportion 4-10 amino acid sequence of SP and is highly specific for both mature SP and extended precursor forms of SP, anti-SP-G that is highly specific for the unamidated COOH-terminal of SP-G, and affinity-purified anti-SP-G-K that is capable of detecting SP-G and minor forms of SP precursor in immunohistochemical analyses. In all examined areas, the content of substance P4-10-like immunoreactivity (SP4-10-LI) quantified by RIA with the use of anti-SP4-10 was greater than that quantified by RIA with the use of anti-SP serum, thereby providing biochemical evidence of steady-state expression of extended precursor forms of SP. Immunohistochemical analyses demonstrated labeled axonal profiles indicating the presence of immunoreactive SP as well as immunoreactive forms of SP precursor within lung hilum and in small fibers in the parenchyma, with no evidence of labeled neuronal cell bodies in these same areas.

Amino Acid Sequence↗

The mucosa mediates tachyphylaxis to leukotrienes C4, D4 and E4 in guinea pig trachea.

Effects of mucosal abrasion on tracheal smooth muscle leukotriene C4, D4 and E4 tachyphylaxis and on histamine contractions before and after four leukotriene exposures were studied. In intact tracheae, leukotriene C4 and E4 second exposure contractions were greater than first. Subsequent contractions showed tachyphylaxis. Leukotriene D4 contractions exhibited progressive tachyphylaxis. Mucosal abrasion potentiated initial leukotriene C4 and D contractions and eliminated leukotriene C4, D4 and E4 tachyphylaxis. Four leukotriene (10(-8) M) exposures reduced histamine (10(-4) M) responses in intact but not abraded preparations. Thus leukotriene C4, D4 and E4 release non-specific inhibitor(s) from tracheal mucosa.

Animals↗

Leukotriene D4 acts in part to contract guinea pig ileum smooth muscle by releasing substance P.

The role of neurotransmitter release in generation of the contractile response to leukotriene D4 (LTD4) by guinea pig ileum longitudinal smooth muscle preparations was studied. The contractile response to LTD4 was inhibited partially by tetrodotoxin (TTx) with early portions of the contraction being more sensitive to inhibition by TTx. This finding suggests that part of the LTD4 contraction is mediated by release of a neurotransmitter as a result of activation of Na+-dependent action potentials. Three approaches, study of the effects of substance P (SP) desensitization and of the effects of a SP antagonist on the LTD4 response and direct measurement of SP release were used to evaluate the possibility that SP is released by LTD4. Partial inhibition of the LTD4 contraction by SP desensitization, and by the SP antagonist, as well as direct measurement of TTx sensitive SP release in the presence of LTD4, indicates that SP is released from neurons by LTD4 in guinea pig ileum.

Animals↗

Hypophosphatemia in infant and adult spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) newborn to three months of age exhibit significantly lower serum inorganic phosphate concentrations than do controls from two normotensive strains, Sprague Dawley (CD) and Wistar Kyoto (WKY). During early postnatal development serum inorganic phosphate increases in all strains and plateaus from eight to twelve weeks. This rise in serum phosphate occurs during a period when blood pressure is increasing in normotensive strains as well as in SHR. Hypophosphatemia even in prehypertensive SHR may relate to elevated parathyroid hormone levels in SHR and may explain the salutary effects of high calcium diets in this hypertensive model.

Animals↗

Distribution of pulmonary cholinergic nerves in the rabbit.

Investigations of the nerves of the rabbit lung, by light and electron microscopy, showed a dense acetylcholinesterase-positive innervation of the bronchi through the bronchiolar level. Large nerve bundles were found to decrease in size as they progressed from extrachondral to subchondral connective tissue, forming complex networks of mostly terminal fibres in the muscle layer. In several instances single fibres penetrated the submucosal layer and approached the mucosa. Gangliocytes, which also reacted positively for cholinesterase, were visible in the vicinity of the large peribronchial bundles. Gangliocytes rarely were seen in association with the vasculature. Blood vessels received a much less dense cholinesterase-positive nerve supply than the bronchi. Single, non-terminal fibres were noted at the adventitiomedial junction of the pulmonary artery and vein. In addition, segments of nerve fibres (networks) were observed in the arterial and venous smooth muscle layers. Cholinesterase-positive innervation was even less extensive in the veins than in the arteries.

Acetylcholinesterase↗

Intranuclear rodlets in a pulmonary neuroepithelial body of a rabbit.

Filamentous intranuclear rodlets were found in a majority of cells in a bronchiolar neuroepithelial body of a rabbit. These rodlets appear to be similar to structures that have been described primarily in neural tissues. They are composed of large bundles of microfibrils made up of smaller subbundles. No close association with any nuclear structure is seen. Although no function can as yet be ascribed to intranuclear rodlets, their demonstration in a neuroepithelial body may be of importance of the understanding of the function of both structures.

Animals↗

Flow-pressure relationships in newborn and infant spontaneously hypertensive rats.

In flow-pressure studies of the perfused "forebody', newborn (3-12 h old) SHR demonstrated significantly lower pressures than newborn WKY at high flow rates. Newborns from dams fed high salt during pregnancy showed no significant differences in flow-pressure relationships from newborns of the corresponding strain whose dams received standard salt. At 2 weeks, SHR continued on standard salt had pressures not significantly different from those of WKY at intermediate and high flow rates. However, 2-week standard salt SHR did demonstrate significantly lower pressures at low perfusion rates than 2-week WKY. 2-week SHR on high salt showed strikingly lower pressures at high flows than 2-week standard salt SHR.

Aging↗

Arterial morphometry in neonatal and infant spontaneously hypertensive rats.

Media/lumen area ratios and density of arteries and arterioles were obtained from tail sections of newborn and 2-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) on prenatal/postnatal high salt diets or standard salt diets. Fixation was by a solution which caused minimal contraction and no differences in contractile response between SHR and WKY. Standard salt SHR of both ages demonstrated significantly greater media/lumen ratios in intermediate size arterioles but not in smaller or larger arterial categories. Prenatal high salt caused significant medial thickening in 49- to 58- micrometer arterioles of newborn SHR. Maintenance on high salt to 2 weeks caused significant medial thickening i SHR arterioles of 19-38 micrometer outside diameter. High salt significantly increased the density of terminal arterioles in 2-week SHR.

Aging↗

Acetylcholinesterase- and norepinephrine- containing nerves in developing rat lung.

The lungs of rat fetuses at various stages of gestation and lungs of infant rats were examined histochemically for acetylcholinesterase (AChE) and norepinephrine (NE). No AChE is present in the fetal lungs until 15 days of gestation. At this stage a number of large round cells appear which stain heavily for AChE. These cells disappear by the 18th day of development and at 18 days no AChE-positive structures are demonstrable within the lung. The large AChE-positive cells are of similar size and distribution to fluorescent cells which become apparent after treatment of the mothers with L-DOPA. At 20 days, the day before delivery, a diffuse AChE reaction appears in the walls of large branches of intrapulmonary bronchi. At 20 days, also, sparse NE-containing nerves are present near the hilum and extend along bronchial arteries into the lung. Not until birth do AChE-containing nerves appear in intrathoracic structures. These are vagal preganglionic and postganglionic fibers near the trachea, bronchi, and esophagus. AChE-positive ganglion cells are present in the walls of extrapulmonary bronchi at birth, and perimuscular nerve plexuses containing AChE are also present in the bronchial walls. NE-containing nerves are visible in several divisions of the bronchial artery at birth. Three days postnatally, AChE-containing nerves have not yet invaded intrapulmonary structures, but at this stage the adult pattern of adrenergic innervation is present. By the fifth postnatal day, sparse AChE-positive nerves are associated with intrapulmonary bronchi, and rats 9 days old present the adult pattern of cholinesterase-containing nerves.

Acetylcholinesterase↗

Release of substance P from guinea pig trachea leukotriene D4.

Coordinated studies of leukotriene D4 (LTD4)-mediated contractile responses and LTD4-evoked release of the tachykinin substance P (SP) in both intact and epithelium abraded guinea pig tracheal smooth muscle preparations were performed. A partial contribution by axon reflex mechanisms to the magnitude of LTD4-induced tracheal contractions was suggested by a maximum inhibition of 21% and 28% by 5 x 10(-6) M tetrodotoxin (TTX) in abraded and intact preparations, respectively. SP-induced contractions were antagonized by the SP analog [DPro4DTrp7,9]-SP 4-11 in both types of preparation. The SP analog produced 58% and 72% inhibition of contractile responses to 10(-8) M LTD4 in abraded and intact preparations, respectively. Direct measurement of SP release by radioimmunoassay of the bathing medium showed TTX-sensitive LTD4-evoked release of SP. Inhibition by 5 x 10(-6) M TTX of LTD4-evoked SP release was 77%. The SP antagonist produced greater inhibition of LTD4-evoked contractions (58% in abraded, and 72% in intact preparations) than maximum TTX inhibition of LTD4-evoked contractions (21% in abraded, and 28% in intact). However, LTD4 (10(-8) M)-evoked SP release was at least 77% blocked by maximum doses of TTX. We therefore suggest that an additional agent, released by TTX-insensitive mechanisms, but whose contractile effects are also antagonized by [DPro4DTrp7,9]-SP 4-11, may participate in the LTD4 response.

Animals↗