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S Vijayaraghavan

Publications and source records attributed to S Vijayaraghavan.

48 records · Page 3Linked to original sources
PubMed1986

Regulation of bovine sperm motility and cyclic adenosine 3',5'-monophosphate by adenosine and its analogues.

Cyclic adenosine 3',5'-monophosphate (cAMP) is known to mediate mammalian sperm function. Progress in understanding the mechanism of the control of cAMP levels in mammalian sperm has been hampered, however, by an inability to identify a physiological regulator of adenylate cyclase. In this report we provide evidence that adenosine, 2'-deoxyadenosine, and a number of other adenosine analogues that activate adenylate cyclase in other tissues stimulate bovine caudal sperm motility, and we suggest that they do so through elevation of cAMP levels. We have demonstrated that these compounds elevate cAMP levels in and stimulate the motility of mature bovine caudal sperm in the same concentration range (20-300 microM). In addition, we report that these same nucleosides, under appropriate conditions, elevate cAMP levels and initiate motility in immature caput sperm. Adenosine analogue structure-activity relationships carried out with caudal sperm indicate that substitution at position 2 in the purine ring in the adenosine molecule leads to enhanced activity, while substitution at the N-6 amino group reduces potency. Nucleosides that do not stimulate motility in caudal sperm do not elevate cAMP levels. We postulate that adenosine is a physiological regulator of sperm motility and suggest that it and its analogues owe their action to elevation of cAMP levels.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Evidence for a role for cellular alkalinization in the cyclic adenosine 3',5'-monophosphate-mediated initiation of motility in bovine caput spermatozoa.

Bicarbonate ion, the local anesthetics procaine and dibucaine, and the ionophores monensin and nigericin have been shown to markedly increase the ability of agents that elevate cyclic adenosine monophosphate (cAMP) levels to initiate motility in bovine caput spermatozoa. A number of other weak bases, including theophylline, D-600 and dipyridamole, elevate cAMP levels maximally in caput sperm at low levels but induce motility only at high levels. These compounds thus appear to have a dual role in the initiation of motility, i.e., they elevate both cAMP levels and internal pH. Confirmation of this view was provided by the demonstration that bicarbonate ion and procaine permit initiation of motility by theophylline, D-600 and dipyridamole at markedly reduced levels. Also, forskolin (a neutral adenylate cyclase activator) elevates cyclic AMP levels in caput sperm but initiates motility only in the presence of bicarbonate or procaine, and the membrane-permeant cAMP analogue 8-bromo-cAMP is capable of inducing motility only in the presence of bicarbonate. Thus, motility in caput sperm is induced only under conditions that elevate both intracellular cAMP and pH, whereas caudal sperm motility is stimulated by an elevation of either cAMP or pH. These data suggest that the epididymal development of motility requires a maturational increase in internal pH. This suggestion was confirmed by direct measurement of the internal pH of caput and caudal sperm; the internal pH of the former was found to be 5.84 +/- 0.1 and the latter 6.27 +/- 0.05.

Animals↗
PubMed1985

Forskolin stimulates bovine epididymal sperm motility and cyclic AMP levels.

Forskolin, a diterpene, has been reported to reversibly stimulate adenylate cyclase from a number of mammalian tissues. Adenylate cyclase preparations derived from sperm are reported to be both deficient in the guanine nucleotide subunit and insensitive to forskolin. Despite the latter observation, we report here that forskolin elevates cAMP levels in immature caput sperm, and initiates motility in the presence of "permissive" agents such as bicarbonate, procaine and dibucaine. In mature caudal sperm forskolin stimulates motility in a concentration dependent manner in the presence of the phosphodiesterase inhibitor IBMX but elevates cAMP levels only briefly before nucleotide levels return to control values. In addition, forskolin stimulates adenylate cyclase activity associated with plasma membrane preparations of caput sperm but not caudal sperm. This differential action of forskolin on these cell types could provide a basis for understanding the regulation of adenylate cyclase in both immature and mature bovine sperm.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Rat mammary tumors from carcinogen-induced nodules and their responsiveness to ovariectomy.

The research objective was to determine whether DMBA-induced rat mammary tumors derived from transplanted mammary nodules differ in ovarian-responsiveness from tumors originating randomly from in situ mammary parenchyma. Nodule-derived tumors were from hyperplastic alveolar outgrowths in mammary fat pads, which were either first generation outgrowths (primary nodule outgrowths) or generations 3-6 of a tumorigenic nodule line (nodule outgrowth T18). Tumors were induced in primary outgrowths by secondary exposure to DMBA in vivo or in vitro. The nodule line was not re-exposed to DMBA because of its high oncogenicity (80-85%). Despite the histological similarity of the tumor derivatives, primary nodule outgrowths and the nodule outgrowth line developed a higher proportion of ovarian-independent to ovarian-dependent tumors (1:3 and 3:4 respectively) than did in situ mammary tissues (1:9). These results are consistent with the observation that nodule outgrowths were themselves ovarian-independent.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Proliferation of ductal outgrowths by carcinogen-induced rat mammary tumors in gland-free mammary fat pads.

The purpose of this study was to evaluate the gland-free mammary fat pad as a preferential site for transplantation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors, since previous studies indicated their frequent failure to grow when transplanted in ectopic sites. Accordingly, samples from 14 primary mammary tumors (9 randomly selected and 5 ovarian-independent) were transplanted into the inguinal pairs of gland-free mammary fat pads of syngeneic female Lewis rats (9-12 wk of age). Although the percentage of takes was high (88%), the growth and morphogenetic capabilities of the transplants were strikingly different. Whereas transplants of ovarian-independent tumors consistently developed palpable carcinomas, transplants of all but 1 of the tumors selected at random (most of which were presumably ovarian-dependent) gave rise mainly to apparently normal ductal and hyperplastic outgrowths. The growth behavior of the transplants could not be correlated with the presence or absence in the tumors of mononuclear cells of the immune system. Unless the mammary fat pad selected against the growth of tumor cells, it seemed that the main alternative to tumor formation by the transplants was the proliferation of nontumorous outgrowths. These results draw attention to differences in the phenotypic stability of primary mammary tumors induced by DMBA and open up for further study the question of whether these differences reflect their cellular heterogeneity or their potential to undergo differentiation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Some aspects of chromosome cytology in the cestode Acanthotaenia multitesticulata.

The diploid chromosome number of the proteocephalid cestode Acanthotaenia multitesticulata is reported for the first time to be fourteen from mitotic as well as meiotic stages of gametogenesis. A chiasma frequency of 2.42 was found. Variation in chromosome numbers in cestodes with reference to this parasite is discussed from an evolutionary point of view.

Animals↗
PubMedDate not supplied

Quantitation of bovine sperm cytoplasmic calcium with Quin-2 and Fura-2: evidence that external calcium does not have direct access to the sperm cytoplasm.

Internal calcium levels of sperm loaded with Quin-2 in the absence or presence of exogenous calcium were 63 +/- 5 and 189 +/- 19 nM, respectively. These values were similar to those determined by Fura-2. Surprisingly, however, dye loaded sperm depleted of internal calcium did not take up calcium from the medium into the cytoplasm upon re-addition of this ion. Uptake was rapid and maximal, however, if these cells were exposed to the calcium ionophores A23187 or ionomycin. Increasing [Quin-2]i progressively lowered [Ca2+]i in spite of the presence of exogenous calcium during dye loading. This anomaly was not due to interference of the fluorophores with calcium uptake, since exogenous 45Ca2+ was taken up at the same rate and to the same extent by control and fluorophore loaded sperm. This 45Ca2+ uptake was mitochondrial and energy dependent. Also, inhibition of mitochondrial calcium accumulation during dye loading lowered [Ca2+]i to values similar to those observed for calcium depleted sperm. These results suggest an extreme impermeability of the sperm plasma membrane to direct calcium entry into the cytoplasm while substantial amounts of calcium entry occurs into the sperm mitochondria.

Adenosine Triphosphate↗
PubMedDate not supplied

Motility potential of macaque epididymal sperm: the role of protein phosphatase and glycogen synthase kinase-3 activities.

Human and monkey ejaculated sperm contain protein phosphatase-1 (PP1), PP1 inhibitor 2 (12), and glycogen synthase kinase-3 (GSK-3). Inhibition of ejaculated human sperm protein phosphatase (PP) activity with calyculin-a (CL-A) significantly stimulates motility, implicating protein dephosphorylation in motility regulation. The present experiments were conducted to characterize and compare PP and GSK-3 activity in monkey caput and caudal epididymal sperm, to determine the cellular distribution of these enzymes, and to test the thesis that epididymal sperm PP activity is inversely related to motility. Caput epididymal sperm populations, (8.8% motile) contained levels of PP activity that were >3 times as high as those of caudal spermatozoa. This PP activity was further identified by inhibitor response profiles as PP1. In both caput and caudal sperm, the majority of this PP1 activity was localized in 100,000 x g soluble fractions. Western blot analysis indicated that a portion of this difference was the result of elevated amounts of PP1 in caput compared with caudal epididymal sperm. The presence of GSK-3 activity was undetectable in 100,000 x g insoluble fractions of epididymal sperm, whereas both caput and caudal sperm soluble fractions contained GSK-3 activity, which was approximately threefold higher in caput sperm compared with caudal populations. Treatment of caput epididymal sperm from the rhesus macaque with the PP inhibitor CL-A resulted in a significant, dose-dependent increase from 8 to 38% motile cells (without any effect on their path velocity). In contrast, CL-A had no significant influence on either percent motility or path velocity of caudal epididymal sperm. Cytosolic PP1 and GSK-3 activities appear to be inversely related to the motility of monkey epididymal sperm and may have a regulatory role in the development of the potential for motility in epididymal sperm.

Animals↗