A new class of potent gastrin antagonists

The hexapeptide Z-Tyr(SO-3)-Met-Gly-Trp-Met-Asp-NH2, from the natural sequence of C-terminal cholecystokinin was found to be a competitive antagonist of cholecystokinin receptors, in vitro. In the present study, we report that this peptide inhibits gastrin-induced acid secretion in vivo, (ED50 = 1.5 mumol . kg-1), without agonist activity. Desulfation of the tyrosine residue slightly altered this effect. The tripeptide Boc-Trp-Met-Asp-NH2 showed similar effects, but had lower potency (ED50 = 12 mumol . kg-1). From these preliminary results, it can be concluded that removal of the phenylalanine residue from the C-terminal sequence of CCK or gastrin, leads to an antagonist of the natural hormones and that C-terminal phenylalanine residue is important for agonist activity. As compared with proglumide, a well known gastrin receptor antagonist, these peptides were 20-200 times more potent as inhibitors on the same model.     

Locomotion and neuromuscular system of Aglantha digitale

Aglantha digitale swims in two ways: a slow rhythmical swim typical of hydromedusae in general and a sudden rapid movement that appears to be an escape response. The swimming musculature is an extremely well developed striated circular muscle layer that possesses a sarcoplasmic reticulum. The nervous system of this species can be divided into three units: an inner nerve ring and an outer nerve ring, which are joined by unusually large transmesogleal pathways, a group of giant axons that extends over the surface of the swimming muscle, and the radial canal. Well developed ciliated sensory cells are located on the exumbrellar surface of the margin. Consideration of these properties of the organisation of this species suggests that normal slow swimming is controlled by a mechanism similar to that found in other medusae, while the escape response is the result of the action of the giant axons.     

Studies of cyclic AMP action using mutant tissue culture cells

Summary S49 mouse lymphoma cell mutants, each with a specific defect in its ability to generate or respond to cyclic AMP, have been isolated. Analysis of the properties of these cells has begun to provide information on complex and significant biologic problems related to the cyclic AMP system. Presented in the Opening Symposium on Nutritional Factors and Differentiation at the 28th Annual Meeting of the Tissue Culture Association, New Orleans, Louisiana, June 6–9, 1977. The work was supported in part by National Science Foundation Grant BMS 75-06764 and National Institutes of Health Grants GM 16496 and GM 00001. P.C. is the recipient of National Institutes of Health Research Career Development Award GM 00308. P. A. I. is an Established Investigator of the American Heart Association.     

The cytosol receptors for progesterone in the different parts of rabbit fallopian tube and uterus during ovum transport

Progesterone receptors were determined in the cytosol from the ampulla, ampullaryisthmic junction and isthmus of rabbit fallopian tube and uterus of estrus and pregnant rabbits. The receptor levels when compared among its various anatomical segments, were the same in ampulla, isthums and uterus but maximum in ampullary-isthmic junction. Significant differences were observed in mated animals at 14, 24, 34, 48, 70 and 144 h after coitus. The receptor concentrations in portions of the fallopian tube showed no significant change between 14 and 24 h after coitus, except for a decrease in ampullary-isthmic junction at 24 h. At 34 h the concentration of receptor further decreased in all parts of the tube. At 48 and 70 h after coitus, receptor concentrations decreased gradually in ampulla and ampullary-isthmic junction, while isthmus showed a gradual increase. At 144 h, the receptor concentration showed no further change in ampulla and ampullary-isthmic junction; however, isthmus showed a decline. The uterine receptor concentration declined steadily from estrus till 70 h after coitus, however, it was increased at 144 h. The dissociation constant (K_d) of cytosol receptor in all the tissues at estrus and during early pregnancy was found similar. The implications of these changes in relation to the normal ovum transport have been correlated in this paper.     

Trypanosoma cruzi: Role of macrophage membrane components in the phagocytosis of bloodstream forms

The phagocytosis of Trypanosoma cruzi bloodstream forms is mediated by macrophage Pronase-sensitive membrane components. Trypsin and chymotrypsin treatment of macrophages, which prevents the uptake of T. cruzi culture forms, does not inhibit the phagocytosis of bloodstream parasites. The phagocytosis activity of the macrophages was recovered within 6–8 hr after the removal of Pronase. Inhibition of protein synthesis after Pronase treatment prevents the recovery of the endocytic activity of the macrophages. Fc and C3b receptors are not apparently essential for the phagocytosis of T. cruzi bloodstream forms. The described membrane components may help to explain the tropism of some T. cruzi strains for cells of the mononuclear phagocytic system in the living host.     

Lack of Fc receptors on osteoclasts

Summary Fc and C₃ receptors, which are characteristically present on macrophages, could not be demonstrated on osteoclasts maintained in situ on their normal substrates when assayed for by use of sheep red blood cells coated with immmoglobulin (Shapiro et al. 1979). The present study tested the hypotheses that Fc receptors are present only on the osteoclast surface adjacent to bone and that Fc receptors on osteoclasts can be uncovered by enzymes or stimulated to appear. Freeze-dried, inverted osteoclasts (and osteoblasts) obtained from the endocranium of newborn rats were tested for Fc receptors using the rosette assay and examined by scanning electron microscopy. No rosettes were observed on the surfaces of the osteoclasts that had been approximal to the bone. Bone specimens were cultured for 30 min at 37° C in control medium, or in medium with the addition of 10, 50 or 100 gmg/ml trypsin, 0.5 U/ml parathyroid extract (PTE), or 0.5 or 1U/ml parathyroid hormone 1–34 (PTH). Additionally, two week-old rats were injected intraperitoneally with PTE (1.5 U/g body weight or 1USP/g body weight) or with PTH (1U/g body weight) or with vehicle alone, 6 h before sacrifice. The specimens were assayed for Fc receptors and examined by scanning electron microscopy. Macrophages were always used as controls for the assay. No rosettes were present on osteoclasts subjected to any of these treatments. Accordingly, the hypotheses were not supported.     

Effects of guanine nucleotides on cns neuropeptide receptors

The effect of nucleotides on central nervous system neuropeptide receptor binding was investigated. The guanine nucleotides, guanosine-5′-triphosphate and guanylyl-5′-imidodiphosphate, significantly inhibited the binding of radiolabeled vasoactive intestinal polypeptide but not that of [Tyr⁴]bombesin to rat brain membranes. Vasoactive intestinal polypeptide binding was inhibited by guanine nucleotides in a dose-dependent manner. Using a 20 μM dose, 60% of the specific vasoactive intestinal polypeptide binding was inhibited by guanylyl-5′-imidodiphosphate, which was more potent than guanosine-5′-triphosphate, whereas other nucleotides were not effective. This reduction in binding was a consequence of lower affinity of the receptor for vasoactive intestinal polypeptide, which in turn resulted from an increased rate of dissociation.     

Opiate receptor antagonism by l-prolyl-l-leucyl-glycinamide, MIF-I

Chronic administration of l-prolyl-l-leucyl-glycinamide (MIF-I) to mice slightly reduced morphine's antinociceptive activity in the hot-plate test and modified the biphasic motor activity response to morphine. MIF-I antagonized the initial depression of activity and potentiated the increased motor activity phase. Chronic treatment of rats with MIF-I prevented morphine's antinociceptive activity in the tail flick test. MIF-I partly antagonized the inhibition by morphine of the coaxially stimulated guinea-pig ileum preparation. The inhibition of the ileum produced by ethylketocyclazocine was weakly antagonized by MIF-I. In contrast, MIF-I had no effect on the inhibition of the stimulated mouse vas deferens produced by Leu-enkephalin. The findings show that MIF-I weakly and selectively inhibits μ-type opiate receptors which suggests that MIF-I could be an endogenous inhibitor of opiate receptors.     

Opiate binding properties of naturally occurring N- and C-terminus modified beta-endorphins

Beta-endorphin is further processed within the pituitary and brain by either N-terminal acetylation, carboxy-terminal proteolysis, or both. These naturally occurring analogues are stored intracellularly and, in some tissues, represent the majority of beta-endorphin immunoreactivity detected by antisera. It is therefore critical to determine their relative potencies at the opiate receptor. This study demonstrates that cleavage of the C-terminus tetrapeptide brings about a 10-fold decrease in opiate binding potency of either camel or human beta-endorphin. N-Acetylation, on the other hand, causes over a thousand fold loss in opiate potency rendering the peptide effectively inactive. Since unmodified beta-endorphin is approximately equipotent at multiple opiate receptors, we tested for possible differential shifts towards mu or delta-type receptors which may result from the modification. Our results show no change in selectivity, but simply an overall loss of potency.     

Sensory cells in the head skin of pond snails

Summary Several types of receptor endings were identified with scanning electron microscopy and silver-impregnation techniques in the skin of the tentacles, lips, dorsal surface of the head and mouth region of the pond snails Lymnaea stagnalis and Vivipara viviparus. Sensory endings at the tips of dendrites of primary receptor neurones, scattered below the epithelium, differ in structure, i.e., the endings exposed to the surface of the skin possess different proportions of cilia and microvilli, which vary in number, length, and packing. Type-I endings have microvilli and a few (1–5) cilia, 5–12 m in length. Type-2 endings have abundant (20–40), interwoven long (9–12 m) cilia and random microvilli. Type-3 endings show typical packing of 10–25 cilia in the form of bundles or brushes. They may be composed either of long (9–18 m) or short (2–7 m) cilia, or of both long and short ones. Microvilli here are absent. Type-4 endings have only microvilli. Two other types of skin receptors do not extend their sensory endings to the surface and can be indentified only in silver-stained preparations. Type-5 endings are branching dendrites of skin receptors cells that terminate among epithelial cells. In type-6, the sensory endings also terminate among epithelial cells but their cell bodies are located outside of the skin. In both species all skin regions examined possess the receptors of all six types differing only in their relative proportion. Possible functional roles of different receptors are discussed.