Variation in guinea pig responsiveness.

Over the years, many reports have been published in which mention has been made of the variation in guinea pig responsiveness due to a number of different influences. In this review, we have attempted to summarize these findings with respect to genetic factors, age, sex, diet, season of the year, infection, and stress.     

Postnatal development of the cerebellar Purkinje cell shape in guinea pig ontogenesis

In sagittal cerebellum sections, morphometrical study of cerebellum of mature-born animals - guinea pigs - was performed using Nissl's procedure. A change of shape and volume of Purkinje cells and their nuclei in the course of the guinea pig postnatal ontogenesis was studied. It has been shown that both the growth process itself and the rate of formation of the definite form of Purkinje cells and of their nuclei in the course of ontogenesis proceeds non-uniformly. The most intensive growth of vertical and horizontal diameters of Purkinje cells and of their nuclei is observed during the 1st and 4th weeks of postnatal life. Especially rapid is an increase of horizontal diameters of Purkinje cells and of their nuclei, which impairs the ovoid-bear-like shape to the cerebellar Purkinje cells of adult guinea pigs.     

Postnatal development of the shape of cerebellar Purkinje cells in guinea pig ontogenesis

In sagittal cerebellum sections, morphometrical study of cerebellum of mature-born animals—guinea pigs—was performed using Nissl’s procedure. A change of shape and volume of Purkinje cells and their nuclei in the course of the guinea pig postnatal ontogenesis was studied. It has been shown that both the growth process itself and the rate of formation of the definite form of Purkinje cells and of their nuclei in the course of ontogenesis proceeds non-uniformly. The most intensive growth of vertical and horizontal diameters of Purkinje cells and of their nuclei is observed during the 1st and 4th weeks of postnatal life. Especially rapid is an increase of horizontal diameters of Purkinje cells and of their nuclei, which impairs the ovoid-bear-like shape to the cerebellar Purkinje cells of adult guinea pigs.     

Postnatal development of "synaptic" ribbons and spherules in the guinea pig pineal gland

Previous studies have shown that the functionally enigmatic pineal "synaptic" ribbons are structurally a heterogeneous group of organelles consisting of rodlike ribbons sensu stricto, spherules, and intermediate forms. As ribbons and spherules react differently under various experimental conditions, these organelles were studied qualitatively and quantitatively during the postnatal period in guinea pigs. It was found that the pinealocytes were highly differentiated at birth and contained all three forms of "synaptic" structures. Ribbons and intermediate forms were more abundant than spherules and exhibited a striking increase in number on postnatal days 1 and 2; this increase was followed by a distinct trough and by a second peak at days 12 and 13, after which their numbers declined to reach adult levels by day 20. The spherules were small in number at birth and did not show the large immediate postnatal increase observed for the ribbons and intermediate forms. Instead there was a steady numerical increase up to day 12 (absolute number) or day 15 (relative numbers), followed by a decrease to adult level by day 20. Whereas during the early postnatal period (days 1 to 3) the majority of pinealocytes were characterized by ribbons and intermediate forms, with increasing age spherule-bearing pinealocytes increased in number. As ribbons and spherules were usually not found in the same pinealocyte, the present findings are interpreted to mean that ribbons and spherules characterize different types of pinealocytes showing an inverse numerical development postnatally. Developmentally intermediate forms behave like ribbons.     

Postnatal development of adrenergic responsiveness in the rabbit heart

It is uncertain how changes in the beta-adrenoceptor population influence the contractility of developing heart. To resolve this we have examined postnatal developmental changes in the adrenergic responsiveness of the rabbit heart. The inotropic effect of isoproterenol on isolated left ventricular papillary muscles from rabbits aged 3, 21, and 90 days was compared with the relative number of beta-adrenoceptors at each age measured using [3H]dihydroalprenolol ([3H]DHA) as the specific ligand. The maximum tension developed in response to isoproterenol increases from 37 +/- 7 to 175 +/- 33% above control twitch tension between 3 and 21 days of age; this is followed by a decrease to 68 +/- 12% in the young adult. During this period of development, there is a decline in EC50 towards increased sensitivity. These differences are partially accounted for by an increase in the numbers of specific [3H]DHA binding sites from 17.3 +/- 2.3 to 56.6 +/- 9.9 fmol/mg wet tissue weight from 3 to 21 days, and a subsequent decrease to 32 +/- 4.5 fmol/mg tissue in the young adult. The proportionally larger increase in contractility compared with the number of beta-adrenoceptor binding sites during the first 3 weeks of life is discussed in terms of the developmental changes in the efficacy of coupling between receptor occupancy and contraction.     

Estrogen responsiveness of fetal guinea pig uterine cells in culture

Cells from the uterus of the guinea pig fetus have been grown as a monolayer culture in serum-containing medium. Cells from the first subculture showed high concentrations of progesterone receptor (PR; 9.3-13.8 pmol/mg DNA) even after 9 days in medium containing charcoal-treated serum and estradiol did not induce any further increase. The antiestrogens, tamoxifen and monohydroxytamoxifen, both had an inhibitory effect which could be overcome by estradiol. The progestins, progesterone and R5020, as well as the antiprogestin, RU38486, also decreased the PR concentration. Estrogen receptor (ER) levels did not vary with the compounds tested but were found to be low compared to concentrations found in the fetal guinea pig uterus at 55-65 days of gestation. None of the compounds tested had any effect on the growth of the fetal uterine cells so that the modulation of PR concentrations was dissociated from the regulation of cell growth. It is concluded that estrogens are necessary but not sufficient factors in the control of PR levels in fetal uterine cells. The establishment of a culture system for separate types of fetal uterine cells will permit us to study in vitro the factors involved in the growth effects of estrogens and the control of PR synthesis.     

Cholinergic responsiveness of intestinal muscle in the pregnant guinea pig

Clinical observations and limited animal experiments have suggested that gastrointestinal motility is suppressed during pregnancy. We therefore compared isometric contractions of colon and ileal circular muscle in response to carbachol (10(-8) to 10(-4) M). Data was analyzed by comparing mean maximal tension, dose-response curves, and EC50 values for tissue from the two groups of animals. Circular muscle from proximal colon, distal colon, and ileum in pregnant animals developed less tension in response to carbachol than did tissue from non-pregnant controls. Dose-response curves in the pregnant groups were depressed, when compared with non-pregnant groups, at concentrations of 10(-6) M and greater. Sensitivity of the muscle to cholinergic stimulation, as measured by EC50 values, was similar in the ileum and proximal colon but increased slightly (p less than 0.05), by a factor of approximately 2, for distal colonic muscle from pregnant animals. Assuming that circular muscle contractions are primarily responsible for mixing and propulsion in the gut, this reduction in responsiveness to excitatory cholinergic stimulation is consistent with the concept of pregnancy-related suppression of gastrointestinal motility.     

Phytohemagglutinin-induced proliferation of guinea pig thymus-derived lymphocytes. II. Accessory cell function.

Accessory cell participation in PHA-induced thymus-derived lymphocyte DNA synthesis encompasses two distinct functions. The first consists of maintenance of the functional integrity of resting lymphocytes, and the second involves the direct induction and/or support of T cell proliferation in response to this mitogen. Whereas the reducing agent 2-mercaptoethanol can support an Mphi-depleted population of resting lymphocytes so that the latent biologic activity is maintained, it is not itself sufficient to allow the induction of lymphocyte proliferation in response to PHA. This latter function requires intact accessory cells.     

Phytohemagglutinin-induced proliferation of guinea pig thymus-derived lymphocytes. I. Accessory cell dependence.

The accessory cell requirement for mitogen-induced T lymphocyte proliferation has been investigated by using a population of guinea pig lymph node lymphocytes enriched in T cells and markedly depleted of macrophages and B lymphocytes. We have found that effective phytohemagglutinin-induced proliferation of T cells is dependent on the participation of accessory cells. Augmentation of PHA responsiveness was noted when cultural conditions were manipulated to increase cell density, suggesting that physical proximity between T cell and accessory cell is required for efficient triggering. Both syngeneic and allogeneic macrophages, as well as syngeneic fibroblasts, serve as accessory cells in this response whereas polymorphonuclear leukocytes or thymocytes do not. Thus, although PHA-induced T lymphocyte proliferation requires accessory cells, the specificity of these cells is strikingly less stringent than for antigen-mediated triggering of immune guinea pig T cells, a response which is dependent upon participation of syngeneic macrophages.     

Internalization of low-density-lipoprotein-specific receptors in leukemic guinea pig lymphocytes

Leukemic guinea pig lymphocytes (L2C) have ten times as many low-density lipoprotein (LDL) receptors as healthy lymphocytes, but LDL accounts for only 38% of the cholesterol in L2C cells, compared to more than 95% in normal cells. Our data show that LDL fails to regulate cholesterol biosynthesis and that there is a defect in LDL internalization and receptor turnover in L2C cells. We also demonstrate that the degradation of LDL is not a limiting process. By discriminating between binding and internalization, we show that internalization in L2C is much slower than in normal cells and that the decrease in metabolism is related to the slow turnover of the LDL receptors.     

Characterization of an antiserum to guinea pig antithrombin III (AT III). I. Reactivity with guinea pig T lymphocytes

In the course of studies investigating the effects of antisera prepared against a variety of guinea pig proteins on lymphocyte function, a goat antiserum prepared against a guinea pig gamma-globulin preparation was found to react with guinea pig T lymphocytes. This antiserum, serum 592, contained a significant titer of antibodies that were cytotoxic for a subpopulation of lymph node cells and thymocytes, and mitogenic for lymph node T cells. Immunoelectrophoretic analysis and selective absorptions of the antiserum demonstrated that the antigen recognized on thymocytes was also present on an alpha 2 globulin in guinea pig plasma, which, on the basis of physiochemical characteristics and heparin-binding affinity, appeared to be guinea pig antithrombin III (AT III). Although the antiserum was shown to contain antibodies to both protein and carbohydrate determinants on the AT III molecule, studies comparing the effects of 7 M guanidine and periodate oxidation on the antigenicity of the AT III determinant also recognized on the thymocytes indicated that this shared antigenic determinant was carbohydrate in nature. The thymocyte membrane molecule bearing this determinant was also isolated and was found to be a 210,000-dalton macromolecule that was very sensitive to proteolytic and/or autolytic degradation. These data raise the interesting possibility that guinea pig lymphoid cells may have a membrane-associated protease inhibitor related to plasma AT III.     

Postnatal development of transport function in the pig intestine

1. In the newborn pig it appears that only prenatally produced enterocytes are capable of absorbing large amounts of protein. 2. The ability of the small intestine to transport sodium, lysine, lysine containing dipeptides and glucose declines markedly during the first week of post natal life. 3. Dexamethosone causes a doubling of the sodium dependent portion of alanine uptake. 4. EGF given between days three and six of postnatal life increases sucrase and maltase activity in the distal region of the small intestine. 5. Weaning induced problems are probably not due to direct inhibition of transport properties.     

Epithelium removal alters responsiveness of guinea pig trachea to substance P

Removal of epithelium from mammalian tracheae has been shown to enhance responsiveness to a variety of contractile and relaxant agents. One of the most dramatic shifts reported has been for guinea pig tracheal tissue denuded of epithelium and treated with substance P. We investigated whether this shift in responsiveness was because of 1) removal of an epithelium-associated enzyme, neutral endopeptidase, which degrades substance P and 2) loss of an epithelium-derived noncyclooxygenase relaxant factor. Using a muscle bath preparation we performed concentration-response curves with substance P and acetylcholine on indomethacin-treated tissues with and without intact epithelium and with and without pretreatment with the neutral endopeptidase inhibitor, phosphoramidon. Epithelium removal potentiated the mean agonist concentration calculated to causes 30% of the maximal contractile response by 148-fold for substance P and by 7-fold for acetylcholine. Phosphoramidon potentiated the contractile response to substance P, but not to acetylcholine, by both the epithelium-intact and denuded tissues (P less than 0.05). However, the degree of enhancement by phosphoramidon was much greater in the intact tissues. With phosphoramidon treatment, therefore, the difference in responsiveness to substance P between the intact and denuded tissues was reduced from 148-fold to 18-fold. This effect of phosphoramidon suggests that the hyperresponsiveness to substance P of epithelium-denuded airway tissue is largely because of removal of neutral endopeptidase. Because all tissues were treated with indomethacin, the leftward shifts in substance P and in acetylcholine responsiveness induced by epithelium removal further suggest that an epithelium-derived noncyclooxygenase factor other than neutral endopeptidase also modulates the contractile response to substance P and to acetylcholine.     

The effect of uremic serum on normal human and guinea pig lymphocytes.

Incubation of normal 51-Cr-labeled human and guinea pig lymphocytes with uremic serum or guanidinosuccinic acid did not cause an increase in 51-Cr release. Electron microscopic examination of these lymphocytes revealed no abnormalities. It is suggested that the lymphocytopenia of uremia is not due to increased destruction of cells but may be a result of redistribution to other body compartments.