Permissive Effect of Insulin-like Growth Factor I (IGF-I) on Gonadotropin Releasing-hormone Action on In Vitro Growth Hormone Release,in Rainbow Trout (Oncorhynchus mykiss)

The aim of the work was to study the influence of insulin-like growth factor I (IGF-I) on GnRH-induced GH release by cultured pituitary cells of normally growing rainbow trout (Oncorhynchus mykiss), collected at different stages of gametogenesis. When pituitary cells were pre-incubated with human IGF-I (10⁻⁸ M) for 48 hours they became responsive to sGnRH (10⁻⁸ to 10⁻⁶ M) in the subsequent 24-hour incubation period, depending on the sexual stage, while not IGF-I pre-incubated cells were always non-responsive to GnRH. The permissive effect of IGF-I was detected in immature fish or those at the beginning of the gametogenesis, but not in mature fish. IGF-I inhibition of GH release during the preincubation period varies also with the sexual stage and is greater in immature than in mature fish. The permissive effect of IGF-I seems specific to somatotropes since IGF-I does not modify GnRH action on GtH₂ release. This work suggests that GnRH action on GH release can vary for a particular fish species depending on the physiological status.     

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates release of somatolactin (SL)-α and SL-β from cultured goldfish pituitary cells via the PAC1 receptor-signaling pathway,and affects the expression of SL-α and SL-β mRNAs

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that stimulates the release of adenohypophyseal hormone from the pituitary in fish. In the goldfish, PACAP induces the release of somatolactin (SL), in particular, from cultured pituitary cells. SL belongs to the growth hormone and prolactin family, and comprises two molecular variants termed SL-α and SL-β in goldfish. However, there is no information about the involvement of PACAP in the regulation of SL-α and SL-β release and the expression of their mRNAs. Therefore, we examined the effect of PACAP on SL-α and SL-β release from cultured goldfish pituitary cells. Treatment with PACAP (10⁻¹⁰–10⁻⁷ M) increased the release of both SL-α and SL-β. The stimulatory action of PACAP (10⁻⁹ M) on SL-α and SL-β release was blocked by treatment with a PACAP-selective receptor (PAC₁R) antagonist, PACAP_(6–38) (10⁻⁶ M). We also examined whether PACAP affects the expression of SL-α and SL-β mRNAs in cultured pituitary cells. Treatment with PACAP (10⁻⁹ and 10⁻⁸ M) for 6 h decreased the expression level of SL-α mRNA but increased that of SL-β mRNA. The action of PACAP (10⁻⁸ M) on SL-β mRNA expression was blocked by treatment with PACAP_(6–38) (10⁻⁶ M), whereas PACAP_(6–38) elicited no change in the expression of SL-α mRNA. These results indicate that in cultured goldfish pituitary cells, PACAP stimulates the release of SL-α and SL-β, and expression of SL-β mRNA, via the PAC₁R-signaling pathway. However, the mechanism whereby PACAP inhibits the expression of SL-α mRNA does not seem to be mediated by PAC₁R signaling.     

The influence of vasoactive intestinal polypeptide and cholecystokinin of prolactin release in rat and human monolayer cultures

We have evaluated the effects of the gut-brain peptides, VIP and CCK, on pituitary PRL secretion in monolayer cultures of normal and tumor bearing rodent and human pituitary tissue. In cultures prepared with normal human pituitary tissue obtained from three patients with metastatic breast cancer, VIP at 10^?7M and 10^?9M (but not 10^?11M) significantly (p<.05) increased PRL secretion in the wells by 6 hrs. Similar concentrations of VIP also significantly (p<.05) promoted PRL release from pituitary tissue obtained by transphenoidal hypophysectomy from one of two prolactinoma patients. Dopamine (10^?5M) inhibition of PRL secretion was not affected by 10^?11 to 10^?7M VIP. In contrast to these findings VIP did not significantly influence 6 hr rat PRL release in monolayer cultures of normal or transformed cells (GH₃) with or without the addition of bacitracin (10^?5M).CCK₃₃ significantly (p<.01) increased rat PRL release in human pituitary monolayer cultures at 10^?5M. The more biologically potent CCK₈ significantly (p<.02) increased rat PRL release at a 10-fold lower concentration, 10^?6M. In contrast, CCK₈ 10^?8 to 10^?6M, did not significantly influence PRL release from normal human pituitary cultures or from tumor bearing human (prolactinoma) and rat (GH₃) cultures. We conclude that 1) the gut-brain peptides, VIP and CCK, can directly stimulate pituitary PRL release and 2) VIP may be a physiologic prolactin releasing factor in man.     

The effects of ghrelin on the in vitro spontaneous and sGnRH-A stimulated luteinizing hormone (LH) release from the pituitary cells of common carp (Cyprinus carpio L.)

In fish, like in mammals, ghrelin affects gonadotropin release acting at the level of the hypothalamus as well as directly on the pituitary gland. In the present study, enzymatically dispersed pituitary cells obtained from sexually mature male and female carp (Cyprinus carpio L.) were incubated in the presence of human ghrelin at the concentration of 10^− 7 or 10^− 6 M, salmon GnRH analogue (Des-Gly¹⁰, D-Arg⁶, Trp⁷, Leu⁸, Pro⁹)-LHRH (sGnRH-A) at the concentration of 10^− 8 M or the combination of ghrelin (both concentrations) and sGnRH-A. ELISA method was used for carp LH levels determination in the media collected after 10 or 24 h of incubation. Ghrelin at the concentration of 10^− 6 M caused the increase of the spontaneous LH secretion from female pituitary cells only. The combination of ghrelin (both concentrations) with sGnRH-A resulted in the significant elevation of LH levels in the incubations of both male and female pituitary cells in comparison with control incubations as well as with sGnRH-A alone treated cells. The results obtained in this study show that ghrelin functions as LH-stimulating hormone in common carp and that it acts directly on gonadotrophic cells, potentiating also the action of GnRH.     

Primary culture of normal pituitary cells of carp (cyprinus carpio) for the study of gonadotropin release

Summary A method for preparing enzymaticlaly dispersed pituitary cell cultures of carp (Cyprinus carpio) is described. The cultures have been used to assay a synthetic analog of gonadotropin releasing hormone (GnRH) and to determine the specificity of steroids able to affect gonadotropin (GtH) release in vitro. Time course secretion studies indicated that by 48 h incubation, in the presence of 500 pM GnRH, cumulative secretion of gonadotropin (719 ng±90/2.5×10⁵ cells) had exceeded that of controls (446 ng±106/2.5×10⁵ cells). Estradiol-17β, progesterone, testosterone, and 11-ketotestosterone showed different inhibitory effects on pituitary basal GtH release. Based on the results, it was concluded that carp pituitary cell cultures can be applied to investigations of several aspects of the hypothalamo-hypophysial-gonadal system. This investigation was supported by the Deutsche Forschungsgemeinschaft, Bonn, FRG.     

The effects of prostacyclin PGI2 on prolactin secretion in vitro

Continuously superfused rat anterior pituitary cells were used to study the effects of exogenous prostaglandins (PGs) and thromboxanes (TXz) on the secretion of prolactin (PRL). No change in hormone release was observed upon superfusion with TXB₂ (10⁻⁵M) or the TX synthesis inhibitor, imidazole (1.5 mM). PGs A2, B2, d2, e1, e2, f1α, F2α, and endoperoxide analogs, U-44069 and U-46619, also had no effect on PRL secretion (all at 10⁻⁵M), In contrast 10⁻⁵M PGI2 was repeteadly found to stimulate PRL release to a level at least 125% above control, while producing no apparent change in the amount of hormone secreted in response to TRH. Somatostatin (SRIF), at a dose of 10⁻M, maximally inhibited TRH-induces PRL output, but failed to alter the PRL response to PGI₂. These studies indicate that PGI₂ may have a direct effect on the anterior pituitary to modify PRL secretion.     

Cholecystokinin octapeptide releases growth hormone from the pituitary in vitro

Cholecystokinin-octapeptide (CCK-8)(10^?6 to 10^?8M) produced a marked increase in growth hormone (GH) release from incubated rat anterior pituitary quarters and from cultured GH₃ pituitary tumor cells. Although several CCK-8 analogues also caused GH release, bombesin, secretin and pancreatic polypeptide had no effect on GH secretion $\text{in vitro}$. In the GH₃ cell line, CCK-8 (10^?7M) reversed the inhibitory effect of somatostatin (10^?5M) on GH release. As CCK immunoreactivity has been demonstrated to be present in the hypothalamus, these results suggest that CCK-8 may be a physiologically important growth hormone releasing factor.     

Different mechanisms are responsible for the contractile effects of histaminergic compounds on isolated intestinal smooth muscle cells

The effects of histamine and dimaprit on intestinal smooth muscle contractility were investigated on isolated cells from longitudinal muscle of the guinea pig ileum. Both histamine (10⁻¹⁴–10⁻¹⁰ M) and dimaprit (10⁻¹³–10⁻¹⁰ M) exerted a concentration-dependent contraction of intestinal cells, causing a maximum decrease in cell length of about 20%. This effect was not significantly different from that induced by cholecystokinin-octapeptide (CCK-8) 10⁻⁹ M. The concentration-response curves to histamine and dimaprit were shifted to the left in the presence of the histamine H₂-receptor antagonist famotidine (10⁻⁷ M) indicating the occurrence in the smooth muscle of H₂ receptors mediating relaxation. Whereas the contraction produced by histamine was competitively antagonized by the H₁ receptor antagonist mepyramine (10⁻⁸ M), neither mepyramine (10⁻⁷ M) nor temelastine (10⁻⁷ M) did modify the contractile effect of dimaprit. In contrast, atropine (10⁻⁸ M) significantly depressed the maximum response to dimaprit without affecting that exerted by histamine. These data indicate that histamine and dimaprit can modify intestinal contractility, by acting via different mechanisms; while the contractile action of histamine is related to H₁ receptor activation, that produced by dimaprit involves cholinergic pathways.     

Stimulatory effect of prostaglandin E1 on thyroliberin-induced α-melanotropin release from perifused neuro-intermediate lobes of frog pituitary gland

A possible direct effect of prostaglandins on α-melanotropin (α-MSH) release at the level of the intermediate lobe of the frog pituitary was investigated $\text{in vitro}$ using a perifusion system technique. The effect of prostaglandins was studied on both spontaneous and TRH-stimulated α-MSH secretion. No significant effect of PGE₁, PGE₂, PGF_1α or PGF_2α on basal release of α-MSH could be detected. Indomethacin did not alter the α-MSH release induced by TRH. Conversely a significant increase in TRH-induced α-MSH secretion was observed in the presence of 1 x 10^?6M PGE₁. This magnifying effect was directly related to the concentration of TRH for doses ranging from 1 x 10^?8M to 1 x 10^?6M.     

Duck Pancreatic Acinar Cell as a Unique Model for Independent Cholinergic Stimulation–Secretion Coupling

This paper investigated the role of acetylcholine (ACh) in physiological regulation of amylase secretion in avian exocrine pancreas. In the isolated duck pancreatic acini, ACh dose dependently stimulated amylase secretion, with a maximal effective concentration at 10 μM. The cAMP-mobilizing compounds forskolin, vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase activating peptide (PACAP) receptor (VPAC) agonists PACAP-38 and PACAP-27 had no effect on the dose–response curve. ACh dose dependently induced increases in cytosolic Ca²⁺ concentration ([Ca²⁺] _c ), with increasing concentrations transforming oscillations into plateau increases. Forskolin (10 μM), PACAP-38 (1 nM), PACAP-27 (1 nM), or VIP (10 nM) alone did not stimulate [Ca²⁺] _c increase; neither did they modulate ACh-induced oscillations, nor made ACh low concentration effective. These data indicate that ACh-stimulated zymogen secretion in duck pancreatic acinar cells is not subject to modulation from the cAMP signaling pathway; whereas it has been widely reported in the rodents that ACh-stimulated exocrine pancreatic secretion is significantly enhanced by cAMP-mobilizing agents. This makes the duck exocrine pancreas unique in that cholinergic stimulus-secretion coupling is not subject to cAMP regulation.     

Effects of dopamine and norepinephrine on in vitro spontaneous and gonadotropin-releasing hormone-induced gonadotropin release by dispersed cells or fragments of the goldfish pituitary

Enzymatically dispersed goldfish pituitary cells or freshly prepared goldfish pituitary fragments continue to secrete gonadotropin spontaneously in a column perifusion system. After the establishment of basal secretion rates, treatment of dispersed pituitary cells with 5 and 500 nM dopamine, or pituitary fragments with 50 and 100 nM dopamine, decreased the amount of gonadotropin released into the perifusate. Perifusion with 500 nM dopamine also abolished the gonadotropin-release response to a 10 nM solution of a luteinizing hormone-releasing hormone analogue in both perifusion systems. Perifusion of pituitary dispersed cells or fragment preparations obtained from sexually regressed goldfish with 50 nM norepinephrine consistently increased the amount of gonadotropin released into the perifusate. These results provide in vitro evidence for direct dopamine inhibition of spontaneous gonadotropin release, blockade by dopamine of gonadotropin-releasing hormone actions, and norepinephrine stimulation of gonadotropin secretion in goldfish.     

Specificity of the stimulatory effect of prostaglandins on hormone release in rat anterior pituitary cells in culture

Specificity of the effect of prostaglandins (PGs) on hormone release by the anterior pituitary gland was studied using cells in primary culture. Growth hormone (GH) release is stimulated by all eight PGs studied, PGE₁ and E₂ being 1000-fold more potent than the corresponding PGFs. The release of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) remains unchanged upon addition of PGEs. While the basal release of thyrotropin (TSH) is only slightly stimulated by concentrations of PGEs above 10⁻⁶M, an important potentiation of the stimulatory effect of thyrotropin-releasing hormone on TSH release is observed. The release of GH, TSH and LH is stimulated equally well by PGAs and PGBs at concentrations higher than 10⁻⁶M, 3 × 10⁻⁶M, and 10⁻⁵M, respectively. PGFs do not affect the release of any of the measured pituitary hormones at concentrations below 10⁻⁴M. The stimulation of GH release by PGE₂ can be inhibited by the PG antagonist 7-oxa-13-prostynoic acid, a half-maximal inhibition being found at a concentration of 4 × 10⁻⁵M of the antagonist in the presence of 10⁻⁶M PGE₂. In the presence of somatostatin (10⁻⁸M), the inhibition of GH release cannot be reversed by PGE₂ at concentrations up to 10⁻⁴M. 8-bromo-cyclic AMP-induced GH release is additive with that produced by PGE₂.The present data show that 1) of the five pituitary hormones measured, only GH release is stimulated by prostaglandins at relatively low concentrations, 2) the PGE-induced GH release can be competitively inhibited by 7-oxa-13-prostynoic acid, 3) the inhibition of GH release by somatostatin cannot be reversed by PGE₂ and 4) the PGEs increase the responsiveness of the thyrotrophs to TRH.     

The apical Na+–HCO3− cotransporter Slc4a7 (NBCn1) does not contribute to bicarbonate transport by mouse salivary gland ducts

The HCO₃ ⁻ secretion mechanism in salivary glands is unclear but is thought to rely on the co-ordinated activity of multiple ion transport proteins including members of the Slc4 family of bicarbonate transporters. Slc4a7 was immunolocalized to the apical membrane of mouse submandibular duct cells. In contrast, Slc4a7 was not detected in acinar cells, and correspondingly, Slc4a7 disruption did not affect fluid secretion in response to cholinergic or β-adrenergic stimulation in the submandibular gland (SMG). Much of the Na ⁺-dependent intracellular pH (pH _i) regulation in SMG duct cells was insensitive to 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid, S0859, and to the removal of extracellular HCO ₃ ⁻. Consistent with these latter observations, the Slc4a7 null mutation had no impact on HCO ₃ ⁻ secretion nor on pH _i regulation in duct cells. Taken together, our results revealed that Slc4a7 targets to the apical membrane of mouse SMG duct cells where it contributes little if any to pH _i regulation or stimulated HCO ₃ ⁻ secretion.     

Antagonism of prostaglandin-promoted pituitary cyclic amp accumulation and growth hormone secretion in vitro by 7-oxa-13-prostynoic acid

The studies reported here confirm the previously observed potent stimulus to growth hormone (GH) secretion by prostaglandin E₁ (PGE₁). Proportional increments in GH secretion were observed following $\text{in vitro}$ addition of PGE₁ over a concentration range of 10^?7 to 10^?5 M. Growth hormone secretion could not be further stimulated by higher concentrations of prostaglandin. Prostaglandin E₁ also increased cyclic AMP concentration in the pituitary explants in a proportional fashion, which correlated closely with its potency as a growth hormone secretogogue. In order to define more precisely the mechanism by which prostaglandin acts, the effects of prostaglandin antagonist, 7-oxa-13-prostynoic acid, on GH secretion and cyclic AMP accumulation were investigated. Addition of the antagonist alone had no consistent effects on GH secretion or cyclic AMP levels in the pituitary. However, the antagonist significantly reduced the stimulation of hormone release and cyclic AMP accumulation found following addition of PGE₁. Increasing the concentration of antagonist further diminished prostaglandin stimulated hormone release and nucleotide accumulation. The antagonist failed to block the stimulatory effects of theophylline and dibutyryl cyclic AMP on GH release, indicating that the inhibition observed occurred prior to intracellular accumulation of the cyclic nucleotide. These results are consistent with the hypothesis that a prostaglandin receptor on the pituitary somatotrope is linked to the adenyl cyclase-cyclic AMP system.     

Activation of Na+ Channels in GH3 Cells and Human Pituitary Adenoma Cells by PACAP

Koshimura, K., Y. Murakami, M. Mitsushima, T. Hori and Y. Kato. Activation of Na⁺ channels in Gh₃ cells and human pituitary adenoma cells by Pacap. Peptides 18(6) 877–883, 1997.—The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on ion channels were examined in GH₃ cells and human pituitary adenoma cells. In GH₃ cells, PACAP-38 (10-9 M) reversibly activated tetrodotoxin-sensitive Na⁺ channels but had little effect on nicardipine-sensitive Ca²⁺ channels. PACAP-induced increase in Na⁺ currents was inhibited by PACAP(6-38), a specific PACAP receptor antagonist, and Rp-cAMPs, an inhibitor for protein kinase A, and mimicked by 8-bromo-cAMP. In human pituitary adenoma cells, PACAP also activated tetrodotoxin-sensitive Na⁺ channels and growth hormone secretion. These results suggest the possibility that PACAP can activate voltage-gated Na⁺ channels via adenylate cyclase-protein kinase A pathway in the pituitary.     

Stimulatory effect of PACAP on gastroduodenal bicarbonate secretion in rats

The effects of pituitary adenylate cyclase activating polypeptides (PACAPs) on gastroduodenal HCO₃⁻ secretion were investigated in anesthetized rats and compared with those of vasoactive intestinal polypeptide (VIP). Under urethane anesthesia, a rat stomach mounted in an ex vivo chamber (in the absence of acid secretion) or a rat proximal duodenal loop was perfused with saline, and the HCO₃⁻ secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Intravenous injection of PACAP-27 stimulated HCO₃⁻ secretion in a dose-dependent manner in the duodenum but not in the stomach; at 8 nmol/kg PACAP-27 increased the HCO₃⁻ secretion to maximal values of four times greater than basal levels, although this peptide had no effect on duodenal HCO₃⁻ secretion after intracisternal administration (1 nmol/rat). PGE₂ (300 μg/kg, iv) significantly increased HCO₃⁻ secretion in both the stomach and the duodenum. The potency of duodenal HCO₃⁻ secretory action was in the following order; PACAP-27 > PACAP-38 = VIP, and that of PACAP-27 was about 100-fold greater than that of PGE₂. The duodenal HCO₃⁻ secretory action of PACAP-27 as well as PGE₂ was markedly potentiated by prior administration of isobutylmethyl xanthine (10 mg/kg, sc), the inhibitor of phosphodiesterase. Folskolin (250 μg/kg, iv), the stimulator of adenylate cyclase, also increased HCO₃⁻ secretion in the duodenum but not in the stomach. These results suggest that: 1) PACAPs are potent stimulators of HCO₃⁻ secretion in the duodenum but not in the stomach; 2) this action is mediated by cAMP through stimulation of adenylate cyclase; 3) cAMP is a mediator in duodenal but not gastric HCO₃⁻ secretion; and 4) PACAPs may be involved in the peripheral regulation of duodenal HCO₃⁻ secretion.     

Oxidative stress caused by pyocyanin impairs CFTR Cl− transport in human bronchial epithelial cells

Pyocyanin (N-methyl-1-hydroxyphenazine), a redox-active virulence factor produced by the human pathogen Pseudomonas aeruginosa, is known to compromise mucociliary clearance. Exposure of human bronchial epithelial cells to pyocyanin increased the rate of cellular release of H₂O₂ threefold above the endogenous H₂O₂ production. Real-time measurements of the redox potential of the cytosolic compartment using the redox sensor roGFP1 showed that pyocyanin (100 μM) oxidized the cytosol from a resting value of − 318 ± 5 mV by 48.0 ± 4.6 mV within 2 h; a comparable oxidation was induced by 100 μM H₂O₂. Whereas resting Cl⁻ secretion was slightly activated by pyocyanin (to 10% of maximal currents), forskolin-stimulated Cl⁻ secretion was inhibited by 86%. The decline was linearly related to the cytosolic redox potential (1.8% inhibition/mV oxidation). Cystic fibrosis bronchial epithelial cells homozygous for ΔF508 CFTR failed to secrete Cl⁻ in response to pyocyanin or H₂O₂, indicating that these oxidants specifically target the CFTR and not other Cl⁻ conductances. Treatment with pyocyanin also decreased total cellular glutathione levels to 62% and cellular ATP levels to 46% after 24 h. We conclude that pyocyanin is a key factor that redox cycles in the cytosol, generates H₂O₂, depletes glutathione and ATP, and impairs CFTR function in Pseudomonas-infected lungs.     

The secretory response in dissociated acini from the rat submandibular gland

Rat submandibular gland was dissociated by enzymatic digestion with collagenase and hyaluronidase, followed by mild mechanical shearing and filtration through a nylon mesh. The dissociated cell populations contained predominantly groups of acinar cells which maintained their acinar arrangement. The morphological and functional viability of the cells was confirmed by electron microscopic examination and a normal secretory response to β-adrenergic or cholinergic stimulation was observed. Both isoproterenol (IPR) and carbachol caused the fusion of secretory granules into large vacuoles which were also continuous with the lumen, and into which the secretory product was released. Secretion was assessed quantitatively from the incorporation of ¹⁴C-glucosamine into the acinar cells and its subsequent release into the culture medium as labelled glycoprotein. IPR stimulated secretion to 125% of untreated controls in the concentration range 5 × 10^?5 to 5 × 10^?7 M, and to 110% of controls at 5 × 10^?8 M, after 40 min incubation. Carbachol stimulated secretion to 131% of controls at 5 × 10^?5 M and to 115% at 5 × 10^?6 M but had no effect at 5 × 10^?7 or 5 × 10^?8 M. The secretory response was blocked by the respective β-adrenergic and cholinergic antagonists, propranolol and atropine. These findings show that dissociated rat submandibular acinar cells provide a useful in vitro model for the study of mucus synthesis and secretion.     

Protein kinase C β1 overexpression augments phorbol ester-induced increase in endothelial permeability

We studied the postulated involvement of the protein kinase C β₁ (PKCβ₁) isoform in the regulation of endothelial permeability using human dermal microvascular endothelial cell line (HMEC-1). We overexpressed the recombinant PKCβ₁ gene via retroviral-mediated transduction in these cells. PKCβ₁ gene transfer was stable, and PKCβ₁ protein production was persistent for at least 1 month posttransduction. Addition of 2 × 10⁻⁹ M and 2 × 10⁻⁸ M phorbol 12-myristate 13-acetate (PMA) to the control (nontransduced) HMEC-1 cells increased the transendothelial ¹²⁵I-albumin clearance rate (an index of endothelial permeability) from 2.5 ± 0.2 × 10⁻² μl/min to 5.4 ± 1.2 × 10⁻² μl/min and 16.8 ± 3.1 × 10⁻² μl/min, respectively. However, addition of 2 × 10⁻⁹ M PMA to PKCβ₁-overexpressing HMEC-1 cells produced a maximal increase in the transendothelial ¹²⁵I-albumin clearance rate of 15.9 ± 2.0 × 10⁻² μl/min. Challenge of these cells with 2 × 10 ⁻⁸ M PMA did not further augment the increase in permeability. Activation with PMA was associated with the translocation of the PKCβ₁ from the cytosol to the membrane. These data show that PKCβ₁ overexpression augments the increase in endothelial permeability in response to PKC activation, suggesting an important function for the PKCβ₁ isoform in the regulation of endothelial barrier. © 1996 Wiley-Liss, Inc.     

Prostaglandins and renin release: I. Stimulation of renin release from rabbit renal cortical slices by PGI2

Prostaglandins have been shown to be involved in the mechanism of renin secretion in a variety of situations. Both arachidonic acid and prostaglandin endoperoxide have been shown to release renin from cortical slices and to be converted to PGI₂ by cortical microsomes. In the present studies PGI₂ was found to cause a time dependent increase in renin release from rabbit renal cortical slices, a system isolated from any indirect effects that result from the administration of prostaglandins . The stimulation was linear up to 30 minutes and effective over a range of concentrations from 10⁻⁷ M to 10⁻⁵ M. At similar concentrations 6-keto-prostaglandin F_1α was not active on these slices. Thus, it is proposed that PGI₂ exerts a direct effect on the release of renin from cortical cells and may be the mediator of arachidonate or prostaglandin endoperoxide stimulated renin secretion.