Lawrence N. Parker

Prostaglandin E2 induces up-regulation of murine macrophage β-endorphin receptors

Cultured murine bone marrow macrophages specifically bound 125I-labeled beta-endorphin. Binding was displaceable by 100 times molar excess of full-length beta-endorphin but was insensitive to the opioid receptor antagonist, naloxone. Binding was inhibited by beta-endorphins C-terminal tetrapeptide, lys-lys-gly-glu, but not by the truncated N-terminal 27 amino acid fragment, indicating that binding of beta-endorphin to this receptor is dependent on its C-terminus. Macrophages incubated for 24 h with 10(-8)-10(-5) M prostaglandin E2 showed a dose-dependent increase in beta-endorphin binding, implying receptor up-regulation. This was also observed in response to the phosphodiesterase inhibitor, isobutylmethylxanthine, indicating that regulation of these receptors may be mediated through a cAMP-dependent process. This is the first demonstration that beta-endorphin receptor expression can be positively regulated.

Angiotensin II potentiates ACTH-stimulated adrenal androgen secretion

Several lines of evidence in animal and human studies, including measurements of elevated adrenal androgens in salt wasting syndromes suggest that adrenal androgen levels may in part be regulated by angiotensin II. This possibility was tested directly by measurement of cortisol and dehydroepiandrosterone (DHA) in canine adrenal cell suspensions after addition of angiotensin II and ACTH, separately and together. Minimal cortisol and no DHA stimulation was obtained using 4 x 10(-10) to 4 x 10(-5) M concentrations of angiotensin II alone. However, increased cortisol and DHA secretion were observed beginning at 4 x 10(-10) M concentrations of angiotensin II when it was combined with 10(-13) MACTH. These are physiological concentrations of both stimuli and may explain the increased adrenal androgens seen in some pathological situations characterized by elevated PRA.

β-endorphin binding in cultured adrenal cortical cells

The polypeptide β-endorphin binds to cultured bovine adrenal cortical cells in a naloxone insensitive manner, β-endorphin and N-Acetyl-β-endorphin are equipotent in inhibiting binding. The amino terminal 27 amino acid fragment referred to as β-endorphin[1–27] shows no ability to inhibit binding, whereas the carboxy-terminal tetrapeptide Lys-Lys-Gly-Glu partially inhibits binding. ACTH, angiotensin II and met-enkephalin show little or no ability to inhibit β-endorphin binding. Competition bin-ding reveals an apparently single affinity class with Kd of 33 nM. Molecular cross linking experiments reveal putative receptor subunits of 85 kD, 64 kD, 54 kD and 44 kD. The lower molecular weight bands are preferentially cross-linked by a hydrophobic cross linking reagent, in contrast to the two higher molecular weight bands, which are cross linked equally by hydrophobic and water soluble cross linking reagents. The β-endorphin binding characteristics of adrenal cortical cells revealed here are quite similar to those of a class of non-opioid β-endorphin receptors previously shown to exist in cells of the immune system.

Hemihypertrophy as possible sign of renal cell carcinoma

In infants and children there is a well-recognized association of hemihypertrophy with visceral malignancies, including those of the kidney as well as benign renal disorders. As a result of our report on an adult with segmental hemihypertrophy and renal cell carcinoma, we suggest that if this combination represents an association similar to that found in children, a radiographic-urologic evaluation is needed to diagnose renal neoplasms at an early stage, and to disclose the presence of treatable benign renal disease.