In order to determine if the newly discovered neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), interacts with the known hypothalamic releasing factors to modulate pituitary hormone secretion, the effect of PACAP, either alone or in combination with either LHRH, TRH, CRF or GHRH, was examined in rat anterior pituitary cell cultures. While PACAP alone weakly stimulated LH and FSH release, PACAP and LHRH, in combination, interacted synergistically to stimulate gonadotropin secretion. No significant changes in the secretion of either TSH, ACTH, or GH were observed in response to PACAP, either alone or in combination with the other releasing factors. Addition of an LHRH antagonist demonstrated that the PACAP effect on gonadotropin release was neither mediated by the LHRH receptor nor the result of LHRH contamination of the PACAP preparation. Because of the sequence homology (68%) between the N-terminal 28 amino acids of PACAP and VIP, the addition of a VIP antagonist was used to demonstrate that the PACAP effect is not mediated through the VIP receptor. The observation that PACAP interacts synergistically with LHRH in stimulating gonadotropin release suggests intriguing possibilities for PACAP in regulating gonadotropin secretion and reproductive function.
Pituitary adenylate cyclase-activating peptide (PACAP), a novel hypothalamic peptide that has been shown to exist in several tissues including the testis, was examined for its effects on cultured rat Sertoli cells. PACAP stimulates cAMP accumulation in Sertoli cells cultured from 15-day-old rats in the presence or absence of methylisobutylxanthine, a phosphodiesterase inhibitor, and in the presence of pertussis toxin, a blocker of the adenylate cyclase inhibitory pathway. Maximal stimulation, which is 20-40% of that attainable with FSH, occurs at PACAP concentrations of 10 nM: the ED50 is approximately 100 pM. The ability of PACAP to stimulate Sertoli cell cAMP declines with increasing age of donor animals (15-60 days of age) in a fashion similar to the FSH effect. PACAP stimulation of Sertoli cell cAMP accumulation is additive with submaximal, but not maximal, concentrations of FSH or forskolin. PACAP also stimulates the secretion of lactate, estradiol, and inhibin in a concentration-dependent manner. The stimulation of Sertoli cell cAMP accumulation by PACAP is not altered by a vasoactive intestinal peptide antagonist, and vasoactive intestinal peptide alone does not stimulate cAMP accumulation, indicating that PACAP is not acting via vasoactive intestinal peptide receptors. Further experiments are needed to determine whether PACAP is synthesized within the testis and if so, in which cell types; however, the present data clearly demonstrate that PACAP can modulate Sertoli cell function in vitro.
Abstract— Benoxaprofen [2‐(4‐chlorophenyl)‐α‐methyl‐5‐benzoxazoleacetic acid] is a phototoxic non‐steroidal anti‐inflammatory agent. Irradiation of human erythrocytes in the presence of benoxaprofen (8 μM) and oxygen resulted in rapid cell lysis which began after 10 min and was complete within 30 min. While photohemolysis was also observed under anerobic conditions, its onset was delayed for more than 20 min and it took nearly 100 min for complete lysis to occur. Photohemolysis was also delayed by butylated hydroxyanisole but was unaffected by reduced glutathione. 1,4‐diazabicyclo[2.2.2]octane, D2O. β‐carotene, or superoxide dismutase. The main photoproduct of benoxaprofen, 2‐(4‐chlorophenyl)‐5‐ethylbenzoxazole, was almost as effective in causing photohemolysis as benoxaprofen itself. In the presence of UV irradiation, benoxaprofen (10 (μM) caused the degranulation of rat peritoneal mast cells and the release of histamine. The release of mast cell histamine may provide a reasonable explanation for the urticarial response to benoxaprofen and irradiation seen in human subjects.
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