Eledoisin stimulation of salivary secretion in dogs

Eledoisin, administered to dogs by intra-carotid route, potently stimulated salivary secretion. The effect was not due to stimulation of cholinergic, adrenergic, histaminergic or 5-hydroxytryptaminergic receptors but was direct on salivary glands.     

Reduced interleukin-1 responsiveness in immune system and central nervous system of inbred polydipsic (STR/N) mice

Inbred polydipsic mice (STR/N strain) have primary polydipsia. The previous studies found abnormalities in the central nervous system (CNS), especially in the hypothalamus and circumventricular organ. As a part of pursuing to find the cause of the polydipsia, we investigated immunological characteristics of STR/N mice, using the ICR strain of mice as control. Their thymic subset cells showed that CD4+CD8+ double positive cells were increased, CD4+ single positive cells were decreased and CD5 expression was deficient, compared to ICR mice. T cell proliferative response and interleukin (IL)-2 production caused by IL-1beta stimulation were reduced in STR/N mice than those in the ICR mice. In in vivo studies the degree of thymic atrophy and the increases in serum level of ACTH and corticosterone induced by intraperitoneal IL-1beta injection were much less in STR/N mice than those in controls. Furthermore, adipsic response also induced by IL-1beta injection was greatly reduced compared to their control mice. All these results suggest that the responsiveness to IL-1 is impaired both in the immune system and the CNS of STR/N mice.     

Cell biology of human salivary secretion

We treated surgical specimens of human parotid and submandibular glands in vitro to manipulate the receptor-signaling cascade pharmacologically and analyzed cellular responses by light microscopy on epoxy embedded sections. Treatment of specimens with the b-agonist, isoproterenol, and with the second messenger analog, dibutyryl cyclic AMP, stimulated serous acinar cells to engage in exocytosis and degranulation. The muscarinic agonist, carbachol, and the calcium ionophore, A23187, on the other hand, elicited formation of "vacuoles" in the cytoplasm of serous acinar cells. Taking previous in vivo human and animal studies into account, these changes are suggested as the morphological expression of enzyme release and fluid secretion, respectively. Specimens obtained from patients over 70 years old exhibited poor response even though their morphological appearance remained intact. Aged salivary glands are thus suggested to experience a decline in their secretory activity at the cellular level, probably by impairment of the signaling processes downstream to the receptor activation and second messenger production.     

Hydronephrosis in the inbred mouse strain DDD

The inbred mouse strain DDD was found to have an extremely high incidence of hydronephrosis (37/37 in adult males and 12/32 in adult females). The hydronephrosis was classified as open with no definite cause for obstruction. The condition was either unilateral in the right kidney or bilateral. Another feature of the hydronephrotic kidney was circulatory failure. Hydronephrosis in strain DDD mice is considered to be a useful experimental animal model with additional possible use, in investigating disturbances of renal haemodynamics and function.     

Codominant expression of genes coding for different sets of inducible salivary polypeptides associated with parotid hypertrophy in two inbred mouse strains

Experimental mouse parotid hypertrophy has been associated with the expression of a number of isoproterenol-induced salivary proline-rich polypeptides (IISPs). Mouse salivary proline-rich proteins (PRPs) have been mapped both to chromosomes 6 and 8. Recently, mice of two inbred strains (A/Snell and A.Swiss) have been found to differ drastically in the IISPs. In this study, mice of both strains were used for cross-breeding experiments addressed to define the pattern of inheritance of the IISP phenotype and to establish whether the IISPs are coded on a single or on several chromosomes. The IISP phenotype of individual mice was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole saliva collected after three daily stimulations by isoproterenol. Parental A/Snell and A.Swiss mice were homogeneous for distinctive strain-associated IISP-patterns. First filial generation (F1) mice obtained from the cross of A/Snell with A.Swiss mice expressed with no exception both the A/Snell and A.Swiss IISPs (coexpression). In the second filial generation (F2) both parental IISP phenotypes reappeared together with a majority of mice expressing the F1-hybrid phenotype (1:2:1 ratio). Backcrosses of F1 x A/Snell and F1 x A.Swiss produced offsprings displaying the F1 and the corresponding parental phenotypes with a 1:1 ratio. No recombinants were observed among F2 mice or among mice resulting from backcrosses. Thus, genes coding for the IISPs that are expressed differentially in both mouse strains are located on the same chromosome, probably at the same locus (alleles) or at quite closely linked loci (nonalleles).     

Pharmacology of serotonin-induced salivary secretion in Periplaneta americana

The acinar salivary gland of the cockroach, Periplaneta americana, is innervated by dopaminergic and serotonergic nerve fibers. Stimulation of the glands by serotonin (5-hydroxytryptamine, 5-HT) results in the production of a protein-rich saliva, whereas stimulation by dopamine results in saliva that is protein-free. Thus, dopamine acts selectively on ion-transporting peripheral cells within the acini, and 5-HT acts on protein-producing central cells. We have investigated the pharmacology of the 5-HT-induced secretory activity of isolated salivary glands of P. americana by testing several 5-HT receptor agonists and antagonists. The effects of 5-HT can be mimicked by the non-selective 5-HT receptor agonist 5-methoxytryptamine. All tested agonists that display at least some receptor subtype specificity in mammals, i.e., 5-carboxamidotryptamine, (+/-)-8-OH-DPAT, (+/-)-DOI, and AS 19, were ineffective in stimulating salivary secretion. 5-HT-induced secretion can be blocked by the vertebrate 5-HT receptor antagonists methiothepin, cyproheptadine, and mianserin. Our pharmacological data indicate that the pharmacology of arthropod 5-HT receptors is remarkably different from that of their vertebrate counterparts.     

NaCl taste thresholds in 13 inbred mouse strains

Molecular mechanisms of salty taste in mammals are not completely understood. We use genetic approaches to study these mechanisms. Previously, we developed a high-throughput procedure to measure NaCl taste thresholds, which involves conditioning mice to avoid LiCl and then examining avoidance of NaCl solutions presented in 48-h 2-bottle preference tests. Using this procedure, we measured NaCl taste thresholds of mice from 13 genealogically divergent inbred stains: 129P3/J, A/J, BALB/cByJ, C3H/HeJ, C57BL/6ByJ, C57BL/6J, CBA/J, CE/J, DBA/2J, FVB/NJ, NZB/BlNJ, PWK/PhJ, and SJL/J. We found substantial strain variation in NaCl taste thresholds: mice from the A/J and 129P3/J strains had high thresholds (were less sensitive), whereas mice from the BALB/cByJ, C57BL/6J, C57BL/6ByJ, CE/J, DBA/2J, NZB/BINJ, and SJL/J had low thresholds (were more sensitive). NaCl taste thresholds measured in this study did not significantly correlate with NaCl preferences or amiloride sensitivity of chorda tympani nerve responses to NaCl determined in the same strains in other studies. To examine whether strain differences in NaCl taste thresholds could have been affected by variation in learning ability or sensitivity to toxic effects of LiCl, we used the same method to measure citric acid taste thresholds in 4 inbred strains with large differences in NaCl taste thresholds but similar acid sensitivity in preference tests (129P3/J, A/J, C57BL/6J, and DBA/2J). Citric acid taste thresholds were similar in these 4 strains. This suggests that our technique measures taste quality-specific thresholds that are likely to represent differences in peripheral taste responsiveness. The strain differences in NaCl taste sensitivity found in this study provide a basis for genetic analysis of this phenotype.     

Inheritance of hydronephrosis in the inbred mouse strain DDD

The mode of inheritance of hydronephrosis was investigated by crossing inbred DDD mice having a high incidence of hydronephrosis and C57BL/6 mice having normal kidneys. In the males, incidences of hydronephrosis in F1 animals were intermediate between the two parental strains at a rate of 32.6% in (DDD x C57BL/6)F1 and 23.4% in reciprocal F1. The same tendency was observed in F2 male animals. In BCF1 males, the number of affected mice was higher in (C57BL/6 x DDD) F1 x DDD (72.4%) than in (DDD x C57BL/6)F1 x C57BL/6 (11.1%). A few affected mice were found among the females of hybrids F1, F2 and BCF1. These results suggested that hydronephrosis in the DDD strain of mice was controlled by polygenes, and that male hormones may have some effect on the occurrence of hydronephrosis.     

Microbiological monitoring in inbred mouse foundation stocks in Japan

Microbiological monitoring on 128 inbred mouse foundation stocks consisted of common 10 inbred strains and inbred strains originated from outbred dd mice was performed by cooperation of 24 organizations. A total of 881 mice were divided into 647 conventional animals from 95 colonies and 234 barrier-sustained animals from 33 colonies. Three viral, one mycoplasmal, 6 bacterial, one fungal and 3 parasitic agents selected as monitoring microbes according to the proposed selection standards. Among conventional colonies, 84.2% were positive for at least one agent. The highest detection rate was 44.2% for S. obvelata, followed by P. pneumotropica and S. muris, P. aeruginosa, G. muris, Sendai virus, M. pulmonis, MHV and E. coli O115a, c: K (B). Of these agents, only one microbe, P. aeruginosa, was detected in barrier-sustained colonies (36.4%), thus the efficacy of barrier system for the microbiological quality control of the inbred mouse foundation stocks was actually demonstrated. The positive rates of MHV (6.3%) and Sendai v. (16.8%) were significantly low compared with those in experimental mouse colonies. Positivity for parasites was rather high and they were infested together with other pathogens in many cases. Thus parasites including G. muris, S. muris and S. obvelata were regarded as useful indicators to see microbiological contaminations in conventional mice. There observed no strain difference in susceptibility to pathogens except for C57BL/6 and AKR mice which seemed to be high antibody responders to MHV.     

Wild-derived inbred mouse strains have short telomeres

Telomere length and telomerase activity directly affect the replicative capacity of primary human cells. Some have suggested that telomere length influences organismal lifespan. We compared telomere length distributions in a number of inbred and outbred established mouse strains with those of strains recently derived from wild mice. Telomere length was considerably shorter in wild-derived strains than in the established strains. We found no correlation of telomere length with lifespan, even among closely related inbred mouse strains. Thus, while telomere length plays a role in cellular lifespan in cultured human cells, it is not a major factor in determining organismal lifespan.