Biomedical subjects

C C Felder

Publications and source records attributed to C C Felder.

76 records · Page 5Linked to original sources

PubMed1989

The dopamine receptor in adult and maturing kidney.

Dopamine, like other neurotransmitters, exerts its biological effects by occupation of specific receptor subtypes. The dopamine receptors in the central nervous system and certain endocrine organs are classified into the D1/D2 subtypes. Outside the central nervous system, the dopamine receptors are classified into the DA1/DA2 subtypes. The D1/D2 and DA1/DA2 receptor have marked similarities and some differences, the most notable of which is the lower affinity of the DA dopamine compared with the D dopamine receptor. DA1 receptor activation increases renal blood flow (RBF); stimulation of DA1 and DA2 receptors may also increase glomerular filtration rate (GFR). DA1 agonists inhibit fluid and electrolyte transport indirectly via hemodynamic mechanisms and directly by occupation of DA1 receptors in specific nephron segments. In the proximal tubule, DA1 agonists simulate adenylate cyclase and inhibit Na+-H+ antiport activity. They also increase phospholipase C and inhibit Na+-K+-ATPase activity (presumably as a consequence of protein kinase C activation). The latter effects may be facilitated by DA2 agonists. In cortical collecting ducts, dopamine antagonizes the effects of mineralocorticoids and the hydrosomotic effect of antidiuretic hormone. It has also been suggested that DA1 may also decrease sodium transport by influencing other hormones, such as atrial natriuretic peptide. Studies of dopamine in the young are complicated because of the propensity for dopamine to stimulate alpha-adrenoceptors. Dopamine alone may actually decrease RBF in the perinatal period. In some animals, the renal vasodilatory and natriuretic effects of dopamine increase with age. Renal tubular DA1-stimulated adenylate cyclase activity increases, whereas renal tubular DA1 receptors decrease with age. Renal DA2 receptor density is greater in the fetus; after birth renal DA2 receptors do not change. Endogenous dopamine may regulate sodium excretion in the young differently than in the adult. In the adult, sodium surfeit is associated with an increase in urinary dopamine; the opposite occurs in the young. A decrease in dopamine production or blockade of dopamine receptors results in an antinatriuresis in the adult; dopamine blockade in the young results in a natriuresis. It remains to be determined whether these age-related differences in dopamine effects are due to changes in receptor DA subtype density, second messengers, and/or interaction with other receptors.

Animals↗

PubMed1989

The dopamine-1 agonist, SKF 82526, stimulates phospholipase-C activity independent of adenylate cyclase.

Dopamine-1 (DA-1) receptors have been found in renal tubular membranes which stimulate both adenylate cyclase and phospholipase-C activity. In renal cortical plasma membrane preparations the DA-1 agonist SKF 82526, forskolin and NaF stimulated adenylate cyclase activity. 2',5'-dideoxyadenosine inhibited basal and DA-1 agonist stimulated adenylate cyclase activity. Forskolin, NaF, dibutyryl-cyclic AMP and 2',5'-dideoxyadenosine had no effect on basal or DA-1 agonist stimulated phospholipase-C activity in these membranes. These studies indicate that DA-1 agonist stimulates adenylate cyclase and phospholipase-C activities independently. Phospholipase-C activity was also increased by the nonhydrolyzable GTP analog, guanosine-5'-O-(3-thiophosphate). When DA-1 agonist and guanosine-5'-O-(3-thiophosphate) were added together there was a slight but significant increase in phospholipase-C activity. This increase was inhibited in the presence of guanosine-5'-O-(2-thiodiphosphate). DA-1 stimulated phospholipase-C activity was found to be insensitive to both cholera and pertussis toxins. The present studies indicate a cyclic AMP independent transduction pathway for DA-1 receptor mediated through a guanine nucleotide regulatory protein associated phospholipase-C.

Adenylyl Cyclases↗

PubMed1987

Severe chloride deficiency in the neonate: the canine puppy as an animal model.

Studies were designed to develop an animal model for the syndrome of hypochloremic, hypokalemic metabolic alkalosis (HMA), and failure to thrive in infants due to intake of chloride-deficient formula. Littermate canine puppies, 2 wk old, were fed soy formula containing normal chloride, 20 mEq/liter (NC, n = 5), or low chloride, 1 mEq/liter (LC, n = 5) for 4 wk, first by gavage and ad libitum thereafter. After 1 wk of LC formula, HMA developed in LC puppies although both NC and LC puppies had similar fluid and caloric intake and gain in weight and forelimb length. Two wk of LC formula also resulted in a higher serum creatinine and calcium but lower phosphate level in LC than NC puppies. After 4 wk of LC, weight and forelimb length were much less in LC than NC puppies. Plasma renin activity decreased with age in NC but remained elevated in LC. In a separate group of puppies (n = 6) with HMA, chloride supplementation of LC formula as NaCl to NC levels corrected HMA despite continued citrate intake. We conclude that the canine puppy is an appropriate model to study HMA due to decreased chloride intake. Low chloride intake independent of citrate caused the HMA.

Alkalosis↗

PubMed1983

Characterization and stabilization of progesterone receptors in human benign prostatic hypertrophy.

Experimental conditions for the optimum detection and measurement of the cytosolic progestogen receptor in human prostatic hyperplasia and neoplasia are described. In presence of 20 mM molybdate ion and a reaction time of 0.5-2 h at 0-2 degrees C, we are able to detect the appearance of a [6.7-3H]-17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione ([3H]-R5020) and [3H]-progesterone binding moiety in human prostatic cytosol. The [3H]-R5020 binding protein sediments at approximately 8-11S in a glycerol density gradient centrifuged in a Sorvall TV865 rotor (vertical rotor). Maximal binding of [3H]-R5020 occurs at 30 min at 25 degrees C and 1 h at 0 degree C. Considerable overall improvement in receptor detection and measurement was made when gradient centrifugation was carried out in a vertical rotor instead of swing bucket rotor. The specifically bound [3H]-R5020 is displaced by progesterone, triamcinolone acetonide and R5020, but not by cortisol, dihydrotestosterone, 17 beta-estradiol, or diethylstilbestrol. High affinity was demonstrated by Scatchard analysis on binding of [3H]-5020 to receptors from cytosol of benign prostatic hypertrophy (BPH) giving a KD of 2.4 X 10(-10)M and a binding site concentration of 50 fmol/mg protein. Molybdate ion maintains the hormone receptor complex in 8-11S form which is totally converted to the 4-5S form in the presence of 0.6 M K Cl. The optimum concentration of fluoride ion for enhancing the specific binding of [3H]-R5020 was determined to be between 20 and 50 mM. Cytosol from human BPH in the presence of 25 mM sodium fluoride contains [3H]-R5020 receptors which sedimented mostly in the 4-5S region of glycerol density gradient. Sodium-molybdate and sodium fluoride stabilize and stimulate the specific [3H]-R5020 receptor complex at 25 and 0 degree C. The loss of specific receptor hormone binding capacity can be reversed by fluoride and, to a lesser extent, by molybdate.

Centrifugation, Density Gradient↗