Abstract
The effects of 3 compounds previously known to alter the adenylate cyclase activity in various tissues were tested on rat pituitary. Forskolin increased while RMI 12,330 A and SQ 22,536 decreased enzyme activity of pituitary homogenates. Forskolin (10(-5) M) promoted in cultured cells a massive synthesis of cyclic adenosine monophosphate (cAMP) and intense output of the nucleotide in the medium; at the same concentration, RMI 12,330 A decreased the cell content of cAMP while release was unaffected, and SQ 22,536 exerted no effect on the cyclic nucleotide amount of both cell and medium. The basal release of plated total cells or enriched gonadotropes was slightly stimulated by forskolin (10(-7) - 10(-5) M) though the level of stimulation never attained the one produced by 10(-7) M luteinizing hormone-releasing hormone (LHRH); it was affected neither by RMI 12,330 A (10(-7) - 10(-5) M) nor by SQ 22,536 (10(-7) - 10(-4) M). The LHRH-stimulating effect was slightly amplified during the 1st h (sensitivity response of cells) by low concentrations of forskolin (10(-7) and 10(-6) M) but the overall luteinizing hormone (LH) release after 4 h of incubation (capacity response of cells) was unmodified. Higher concentrations of the diterpene inhibited the LHRH effect as seen with total cells and with enriched gonadotropes. RMI 12,330 A at 10(-5) M significantly inhibited the LHRH-promoted LH release from total cells and from gonadotropes but a higher concentration (10(-4) M) promoted a large unspecific release that masked the LHRH effect. SQ 22,536 never modified the cell response to LHRH, whatever the drug concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Published Version
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