Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (AII) stimulates capacitation and fertilizing ability in mammalian spermatozoa, with the binding of AII to its receptors resulting in stimulation of cAMP production in both uncapacitated and capacitated cells. This study investigated possible mechanisms whereby AII affects cAMP availability. The first question was whether extracellular Ca2+ is required for responses in mouse spermatozoa and, using chlortetracycline fluorescence analysis, it was clear that cells responded to AII only when the medium contained CaCl2, with both 90 microM and 1.80 mM supporting a significant acceleration of capacitation. Consistent with those results, AII significantly stimulated cAMP production in both CaCl2-containing media tested, the response being greater in that containing 1.80 mM. Several different agents that might affect the signalling pathway stimulated by AII were then evaluated in uncapacitated suspensions. Chlortetracycline analysis revealed that pertussis toxin abolished responses to AII, suggesting the involvement of an inhibitory Galpha subunit; dideoxyadenosine, a specific membrane-associated adenylyl cyclase (mAC) P-site inhibitor, also blocked responses, suggesting involvement of an mAC. cAMP determinations confirmed that both reagents also abolished AII's stimulation of cAMP. In contrast, nifedipine, a Ca2+ channel blocker, did not inhibit AII's effects on spermatozoa. Finally, in capacitated suspensions, both pertussis toxin and dideoxyadenosine were again shown to block AII's stimulation of cAMP. These results suggest that responses to AII involve an inhibitory G protein and an mAC, but it is likely that AII-receptor coupling does not stimulate directly mAC but rather does so in an indirect manner, perhaps by altering the intracellular Ca2+ concentration.
 ...
PMID:Mechanisms of action of angiotensin II on mammalian sperm function. 1569 15

We investigated, using guinea-pig spermatozoa as a model, whether phospholipase A2 (PLA2) is involved in progesterone or zona pellucida (ZP)-stimulated acrosomal exocytosis, if progesterone enhances ZP-induced activation of PLA2, and mechanisms underlying PLA2 regulation. Spermatozoa were capacitated and labeled in low Ca2+ medium with [14C]choline chloride or [14C]arachidonic acid, washed, and then exposed to millimolar Ca2+ and progesterone and/or ZP. Each agonist stimulated decrease of phosphatidylcholine (PC) and release of arachidonic acid and lysoPC, indicative of PLA2 activation. Aristolochic acid (a PLA2 inhibitor) abrogated lipid changes and exocytosis, indicating that these lipid changes are essential for exocytosis. Exposure of spermatozoa to submaximal concentrations of both progesterone and ZP resulted in a synergistic increase of arachidonic acid and lysoPC releases, and exocytosis, suggesting that, under natural conditions, both agonists interact to bring about acrosomal exocytosis. Progesterone-induced PLA2 activation appears to be mediated by a GABA(A)-like receptor, because bicuculline (a GABA(A) receptor antagonist) blocked arachidonic acid release and exocytosis. In agreement with this, GABA mimicked progesterone actions. ZP-induced activation of PLA2 seemed to be transduced via G(i) proteins because pertussis toxin blocked arachidonic acid release and acrosomal exocytosis. PLA2 may be regulated by PKC because progesterone- or ZP-induced release of arachidonic acid was blocked by the PKC inhibitors staurosporine or chelerythrine chloride. PLA2 could also be regulated by the cAMP-PKA pathway; inclusion of the PKA inhibitor 14-22 amide or H-89 led to a reduction in arachidonic acid release or exocytosis after progesterone or ZP. Taken together, these results suggest that PLA2 plays an essential role in progesterone or ZP-stimulated exocytosis with progesterone priming ZP action.
 ...
PMID:Progesterone primes zona pellucida-induced activation of phospholipase A2 during acrosomal exocytosis in guinea pig spermatozoa. 1596 49

To explore the biological characteristics of the recombinant zona pellucida 3 (ZP3) peptides of rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348, we examined whether rhuZP3a22 approximately 176 or rhuZP3b177 approximately 348 trigger the acrosome reaction (AR) of human spermatozoa and we investigated the underlying mechanism. The assessment of AR was performed using chlortetracycline staining. The intracellular free calcium concentration ([Ca2+]i) in Fura-2/AM-loaded human sperm was monitored with a spectrofluorophotometer. We found that rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 were capable of eliciting AR at different concentrations. With the addition of either peptide, the [Ca2+]i level was raised to a peak with or without a plateau. The AR could be inhibited by pertussis toxin (PTX), EGTA, and pimozide (a T-type calcium channel blocker), whereas verapamil was less effective in this regard. The results of the present study suggest that peptides rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 have a role similar to human ZP3, and that the mechanism of the response to the peptides involves influx of calcium, the G protein pathway, and a T-type calcium channel.
 ...
PMID:Acrosome reaction induced by recombinant human zona pellucida 3 peptides rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 and their mechanism. 1719 98

A translucent matrix termed the zona pellucida (ZP) surrounds the mammalian oocyte. It plays a critical role in fertilization by acting as a "docking site" for binding of spermatozoa followed by induction of the acrosome reaction in the zona bound sperm. Recent analyses of the genes of the human oocyte revealed that the ZP matrix is composed of four glycoproteins, designated as ZP1, ZP2, ZP3 and ZP4, instead of 3 found in the mouse ZP. Comparison of the deduced amino acid (aa) sequences of the human ZP glycoproteins with those from various species, revealed that these are evolutionarily conserved. Phylogenetic analysis revealed that ZP1 and ZP4 may be related as these have the highest sequence identity at the aa level within a given species. Each zona protein has a signal sequence driving these proteins to the endoplasmic reticulum, a aproximately 260 aa long 'ZP domain' comprising of 8-10 conserved cysteine residues, a C-terminal, hydrophobic transmembrane-like region and a short cytoplasmic tail. In order to understand the structure-function relationship of human ZP glycoproteins, our lab has cloned and expressed ZP2, ZP3 and ZP4 proteins both in E. coli as well as baculovirus expression systems. Simultaneously, our group has been able to amplify the cDNA encoding human ZP1. Employing baculovirus-expressed recombinant ZP glycoproteins; our group has provided evidence for the first time that in human, in addition to ZP3, ZP4 is also able to induce acrosomal exocytosis in the capacitated spermatozoa. ZP3 mediated induction of the acrosome reaction can be inhibited by pertussis toxin suggesting the involvement of G, protein in downstream signaling in contrast to ZP4, which follows a G, protein independent pathway. Hence, elucidation of the role of individual ZP glycoproteins in humans will provide a better insight into the gamete interaction culminating in fertilization.
 ...
PMID:Structural and functional attributes of zona pellucida glycoproteins. 1756 74

Progesterone has an extragenomic action on human spermatozoa characterised by the rapid induction of a calcium transient followed by a plateau phase during which [Ca2+], remains significantly above baseline. By imaging the calcium responses generated in individual cells, we have demonstrated that during this plateau phase, spermatozoa exhibit a series of asynchronous secondary calcium oscillations. The incidence of such oscillations was dependent upon sperm capacitation and showed significant inter-individual variation. The oscillations were dependent upon the influx of extracellular calcium via mechanisms that were insensitive to inhibitors of L-type voltage operated calcium channels (nifedipine, verapamil, diltiazem), G-proteins (pertussis toxin) or the GABA (A) receptor (bicuculline). However, treatment with an inhibitor of the GABA-associated chloride channel (picrotoxin) significantly suppressed the incidence of secondary calcium oscillations in pentoxifylline-treated cells, as did two inhibitors of T-type calcium channels (pimozide and amiloride). We hypothesise that the sub-population of spermatozoa exhibiting secondary calcium oscillations are characterised by a hyperpolarized plasma membrane that sets T-type channels in a closed but activation-competent state. The secondary calcium oscillations created via these channels do not induce acrosomal exocytosis per se but may prime the cells so that this event is rapidly triggered when the spermatozoa make contact with the zona pellucida.
 ...
PMID:Molecular mechanisms of sperm capacitation: progesterone-induced secondary calcium oscillations reflect the attainment of a capacitated state. 1756 79

Mammalian fertilization is initiated by species-specific binding of the sperm to the zona pellucida, or egg coat. Previous studies suggested that sperm adhesion to the egg coat is facilitated, at least in part, through the binding of sperm surface beta1 ,4-galactosyltransferase I (GaIT) to glycoside chains on the egg coat glycoprotein, ZP3. Binding of multiple ZP3 oligosaccharides induces aggregation of GaIT within the sperm membrane, triggering, directly or indirectly, a pertussis toxin sensitive G-protein cascade leading to induction of the acrosome reaction. Consistent with this, spermatozoa bearing targeted deletions in GaIT are unable to bind ZP3 or undergo ZP3-dependent acrosomal exocytosis; however, unexpectedly, GaIT-null sperm are still able to bind to the egg coat. This indicates that sperm-egg binding requires at least two independent binding mechanisms; a GaIT-ZP3-independent event that mediates initial adhesion, followed by a GaIT-ZP3 interaction that facilitates acrosomal exocytosis. Our recent efforts have focused on the identification and characterization of these novel gamete receptors. One recently identified sperm protein that is required for sperm adhesion to the egg coat is SED1. SED1 is a bimotif protein composed of two Notch-like EGF repeats and two discoidin/complement F5/8 domains. SED1 is secreted by the epididymal epithelium and coats spermatozoa as they progress through the epididymis. Spermatozoa null for SED1 fail to bind the egg coat, illustrating its requirement for gamete adhesion. Interestingly, SED1 is also expressed by a variety of other epithelial tissues, where it appears to be required for epithelial morphogenesis and/or maintenance. A second novel gamete receptor has recently been identified on the coat of ovulated oocytes. This ZP3-independent, egg coat component is a high molecular weight, wheat germ agglutinin (WGA)-reactive glycoprotein that is derived from oviduct secretions and appears to participate in initial sperm adhesion. The amino acid sequence of this oviduct-derived ligand is currently being determined for the generation of peptide-specific antibodies and for the creation of knock out mice. The identification of novel gamete receptors that are required for sperm-egg binding opens up new avenues for the development of specific contraceptive strategies.
 ...
PMID:Novel gamete receptors that facilitate sperm adhesion to the egg coat. 1756 85

There is evidence that ergot alkaloids can directly interact with mammalian spermatozoa affecting sperm functions. Ergot alkaloids exert their toxic or pharmaceutical effects through membrane receptor-mediated activities. This study investigated the signaling pathways involved in the in vitro inhibitory effects of both ergotamine (ET) and dihydroergotamine (DEHT) on the relative motility of bovine spermatozoa using specific inhibitors. Motile bovine spermatozoa were prepared using a Percoll gradient and incubated with ergot alkaloids with and without signaling pathway inhibitors. Co-incubation of ET or DHET with 100 microM prazosin (alpha 1-adrenergic receptor inhibitor) decreased (p < 0.05) relative motility of spermatozoa when compared with controls. In addition, preincubation of spermatozoa with 10 or 20 microM prazosin and DHET also reduced (p < 0.05) the number of motile spermatozoa. Relative sperm motility (motility of treated spermatozoa normalized to control sperm motility) was increased (p < 0.05) when co-incubations included ET and yohimbine (alpha 2-adrenergic receptor inhibitor); conversely, co-incubation of yohimbine (100 microM) and DHET decreased (p < 0.05) the percentage of motile spermatozoa when compared with controls. Pertussis toxin and cholera toxin (effectors of inhibitory and stimulatory G-proteins, respectively) altered (p < 0.05) relative sperm motility in a concentration dependent manner; however, co-incubation of pertussis or cholera toxin with ergot alkaloids had no interactive (p = 0.83) effects on the relative motility of spermatozoa. Co-incubation of Rp-cAMP (a membrane-permeable cAMP inhibitor) with 50 microM DHET had no effect (p > 0.05) on relative sperm motility; whereas, the co-incubation of 22.4 or 44.8 microM Rp-cAMP with 50 microM ET increased (p < 0.05) the percentage of motile spermatozoa when compared with 0 or 224 microM Rp-cAMP (49%, 65%, 59%, and 54%, respectively, for 0, 22.4, 44.8, and 224 microM of Rp-cAMP. An interaction between BAPTA-AM (a chelator of intracellular calcium) and alkaloids also impacted (p < 0.05) relative sperm motility. Generally, co-incubating spermatozoa with BAPTA-AM and ET increased the percentage of motile spermatozoa; however, co-incubation with DHET decreased relative sperm motility except with 41 microM BAPTA-AM. Collectively, these observations suggest that ET and DHET decreased the percentage of motile bovine spermatozoa via alpha adrenergic receptors. However, the second messenger systems involved with ergot alkaloid inhibition of relative motility of bovine spermatozoa remain to be elucidated.
 ...
PMID:Involvement of signaling pathways in bovine sperm motility, and effect of ergot alkaloids. 1945 32

Haploid germ cells (spermatids and spermatozoa) develop in the testis after immune tolerance has been established. Therefore, they contain various autoimmunogenic antigens, but the testis is known to be an immunologically privileged organ. In particular, the blood-testis barrier formed by Sertoli cells protects autoimmunogenic haploid germ cells from attack by the autoimmune system. Experimental autoimmune orchitis (EAO), a breakdown of the testicular immune privilege leading to immunological male infertility, has been ordinarily induced in mice by immunization twice with testicular antigens+complete Freund's adjuvant (CFA)+Bordetella pertussis (BP). We previously found that two subcutaneous injections of viable syngeneic testicular germ cells induced murine EAO without the use of CFA+BP. In both EAO models, the lesions are characterized by spermatogenic disturbance with lymphocytic inflammation, and a second immunization with testicular antigens is critical for the disease induction. In the present study, we found that only one placement of a syngeneic donor's testes, epididymides and vasa deferentia (TEV) into the abdominal cavity or subcutaneous space was sufficient to induce EAO on the recipient's testes in mice. It was also noted that the placement of TEV induced only orchitis without epididymo-vasitis, while the serum autoantibodies were reactive with haploid germ cells existing throughout the TEV. Furthermore, the TEV placed in the abdominal cavity rather than the subcutaneous space was effective in inducing severe EAO, and the A/J strain was most susceptible to the TEV-induced EAO among the three strains examined. The model of EAO induced by the placement of the donor's TEV into the abdominal cavity in A/J mice will be helpful for the further analyses of testicular autoimmunity.
 ...
PMID:Experimental model of autoimmune orchitis with abdominal placement of donor's testes, epididymides, and vasa deferentia in recipient mice. 2172 65

Fertilization is indispensable for zygotic formation leading to the birth of animals and the species-specific sperm-egg binding thought to be the initial step in this important process. In birds, the oocyte, which encounters the spermatozoa at the time of fertilization, is enclosed in a perivitelline membrane (pvm) constructed of several zona pellucida glycoproteins (ZP proteins: ZP1, ZP2, ZP3, ZP4 and ZPD). The aim of this study was to determine the ZP protein in the pvm responsible for sperm-pvm binding in Japanese quail. We tested the effects of anti-ZP protein antibodies on in vitro sperm perforation in the pvm. The results showed that the anti-ZP1 and ZP3 antibody significantly blocked hole formation by sperm, whereas anti-ZP2, ZP4 and ZPD as well as normal rabbit serum had no such effect. When the sperm acrosome reaction was inhibited in the presence of pertussis toxin, sperm-pvm binding was observed. This sperm-pvm binding was significantly prevented when the purified ZP1 or ZP3 was included in the reaction mixture. Moreover, both digoxigenin-labeled ZP1 and ZP3 were found to interact with the sperm head by immunocytochemical observation. Our results indicate that sperm binding to the pvm is, at least in part, mediated by the interaction of ZP1 and ZP3 with the sperm head during fertilization in Japanese quail.
 ...
PMID:Egg Envelope Glycoproteins ZP1 and ZP3 Mediate Sperm-Egg Interaction in the Japanese Quail. 3290 12


<< Previous 1 2 3