Endothelin stimulates short circuit current in a cultured epithelium

Previous studies reported that epididymis contains functional LH receptors. The LH receptor knockout mice, which have epididymal phenotypes, gave us an opportunity to test the hypothesis that testosterone replacement alone may not be sufficient to reverse phenotypes to wild-type epididymis. The morphological phenotype in knockout animals includes a decrease in luminal diameter of the proximal and distal caput and cauda epididymis, the absence of clear and halo cells in the epithelial lining, a decrease in the height of principal cells and the number of cells containing cilia, a decrease in cilia length, and a change from basal to central location of nuclei in the principal cells. The biochemical phenotype includes a decrease in periodic acid-Schiff reaction product, reflecting the glycogen and glycoprotein synthesis and secretion, a decrease in androgen receptor (AR) and estrogen receptor (ER)beta, and an increase in ERalpha levels. Twenty-one-day testosterone replacement therapy in 30-day-old knockout animals reversed some, but not all, morphological and biochemical phenotypes. Those that did not reverse include luminal diameters of proximal and distal caput and cauda epididymis, the percentage of ciliated principal cells in caput epididymis, and nuclear AR localization. In summary, while our results reaffirm that androgens are important for normal epididymal morphology and function, they indicate that LH could be required for certain facets of epididymal morphology and/or function.

Section: Discussionmentioning

confidence: 99%

Epididymal Phenotype in Luteinizing Hormone Receptor Knockout Animals and Its Response to Testosterone Replacement Therapy1

Lei

Zou

Mishra

et al. 2003

“…3, lower panel). These results show that, as with other peptide hormones viz., angiotensin [21], bradykinin [17], CGRP [32], endothelin [22], and PACAP [7], secretin regulates anion and fluid transport in the epididymis.…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has shown that angiotensin [21], bradykinin [17], and endothelin [22] stimulate chloride secretion by increasing formation of prostaglandins. Experiments were performed on epithelia pretreated with piroxicam, an inhibitor of prostaglandin synthesis, before stimulation with secretin, PACAP, or bradykinin.…”

Section: Effects Of Cox and Adenylate Cyclase Inhibitorsmentioning

confidence: 98%

Secretin Controls Anion Secretion in the Rat Epididymis in an Autocrine/Paracrine Fashion1

Chow

Cheung

Tsang

et al. 2004

Self Cite

There is growing evidence that secretin, the first hormone discovered in our history, has functions in the brain other than in the gastrointestinal tract. This article reports for the first time that secretin and its receptor mRNAs are produced in distinct cell types within the epididymis. To test if secretin affects electrolyte transport in the epididymis, we measured short-circuit current (Isc) in cultured epididymal epithelia and found secretin dose-dependently stimulated Isc. Ion substitution experiments and use of pharmacological agents inferred that the stimulated Isc is a result of concurrent electrogenic chloride and bicarbonate secretion. It is further shown that secretin and pituitary adenylate cyclase-activating polypeptide (PACAP) function via totally different mechanisms: 1) PACAP works only from the apical side of the epithelium to stimulate chloride and not bicarbonate secretion, while secretin acts on the apical and basolateral sides to stimulate chloride and bicarbonate secretion. 2) the stimulation by PACAP but not secretin requires local prostaglandin synthesis. By immunocytochemical staining, secretin is localized in the principal cells of the initial segment and caput epididymidis, whereas secretin receptor is present in the principal cells of the proximal as well as the distal part of the epididymis. This pattern of distribution appears to be consistent with the idea that secretin is secreted by the proximal epididymis and acts on the proximal and distal epididymis in an autocrine and paracrine fashion. Its function is to control secretion of electrolytes and water.

“…Previous work has shown that Cl-secretion is principally responsible for the Isc in the cauda epididymal epithelium [9,10]. In the present study, a C1-channel blocker, DPC [11,12], and Cl--free solution (substituted with gluconate) were employed to investigate the involvement of C1-.…”

Section: Bioelectrical Properties and Anion Secretion In Rats Basal Iscmentioning

confidence: 96%

Regional Differences in Bioelectrical Properties and Anion Secretion in Cultured Epithelia from Rat and Human Male Excurrent Ducts1

Chan

Lai

et al. 1995

Self Cite

Bioelectrical properties and anion secretion in cultured epithelia from different regions of rat and human male excurrent ducts were studied by measuring the short-circuit currents (ISC). In all regions of the rat excurrent duct, Cl- secretion accounts for over 90% of the basal ISC, although the magnitude varied in different regions. Cl- secretion was found to be mediated by a Cl-/HCO3- exchanger, an Na+/H+ exchanger, and an Na+/K+/2Cl- symport located on the basolateral side of the epithelial cells. Forskolin, an activator of adenylate cyclase, and ionomycin, a Ca2+ ionophore, were used to investigate the relative importance of cAMP and Ca2+ as intracellular messengers regulating Cl- secretion in different regions. It was found that in both species, the forskolin-evoked ISC response was larger in the proximal end (efferent duct/caput epididymidis [rat/human, respectively]) than in the distal end (cauda/corpus epididymidis). The response to ionomycin in the rat cauda epididymidis (distal end) was larger than that in the efferent duct (proximal end); on the other hand, no significant difference in the ionomycin-induced ISC was observed in the caput and the corpus regions from the human epididymis. Our results indicate that while the cAMP- and Ca(2+)-dependent pathways are both involved in regulating Cl- secretion in all regions along the male excurrent ducts in both species, a regional difference exists with respect to the relative importance of the two regulatory pathways involved in Cl- secretion along the male reproductive tract.