In vitro activity and selectivity of glucosidic SP(6-11) analogues

The relative potencies of a series of substance P (6-11) analogues have been determined for spasmogenic activity in the guinea pig ileum in vitro and for potentiation of electrically evoked contractions in the rat vas deferens in vitro. ED50 values were determined for the new analogues. Substance P and its methyl ester were used as standard agonists. Substitution of Gly9 by Pro on [Glu6]SP(6-11) increased four times the activity on the NK-1 receptor. The glycosilation of [Glu6]SP(6-11) by the incorporation of a beta-D-glucopyranosyl amide residue on the gamma-carboxyl group of Glu6 reduced both the activity and selectivity. The simultaneous substitution of Gly9 by Pro and the incorporation of a monosaccharide moiety on the gamma-carboxyl of Glu6 on [Glu6]SP(6-11) yielded an analogue with 60-fold enhanced selectivity relative to substance P for the NK-1 receptor. These results may indicate that the critical factor providing potency to SP(6-11) analogues is mostly related to conformational rather than hydrophilicity aspects of the molecular structure.     

Programs for radioimmunoassays and radioreceptorassays using SPSS-X

Two sets of programs written using SPSS-X, and designed for the analysis of data obtained by radioimmunoassay or radioreceptorassay are presented. The main advantages of the programs are that they are easily edited, their commands are simple and logical, and they can be used for any type of radioimmunoassay or radioreceptorassay, respectively. The programs for radioimmunoassay can also be used for fluorescenceimmunoassay and luminescenceimmunoassay.     

Effects of Estrogen and Ectopic Pituitary Transplants on the Responsiveness of Pituitary Prolactin Release to Luteinizing Hormone-Releasing Hormone and Dopamine

The responsiveness of prolactin release to regulatory inputs depends on the functional state of the lactotrophs. In the present study, we have examined the effects of luteinizing hormone-releasing hormone (LHRH; 10^–7 or 10^–6 M) on the release of prolactin in vitro from hyperplastic pituitaries of estrogen-treated male Fischer rats, ectopic pituitary transplants and in situ pituitaries of grafted and control rats. The effects of dopamine (10^–8 or 10^–7 M) in this system were also examined. The extent of inhibition of prolactin release by dopamine was not related to the amounts of prolactin secreted under basal conditions or to plasma prolactin levels. LHRH significantly suppressed prolactin secretion in all groups but its effect was most pronounced in the ectopic pituitary transplants and in the hyperplastic pituitaries of animals after chronic exposure to estrogen followed by a period of recovery. Thus, the effects of LHRH on prolactin release appear to be related to the secretory activity and/or to the absolute or relative number of the lactotrophs.