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M Díaz-Hernández

Publications and source records attributed to M Díaz-Hernández.

10 recordsLinked to original sources
PubMed2006

Role of CaCMKII in the cross talk between ionotropic nucleotide and nicotinic receptors in individual cholinergic terminals.

Ionotropic P2X receptors for ATP are formed, to date, by seven different subunits named P2X (Torres et al., 1999; Cunha and Ribeiro, 2000; North and Surprenant, 2000; Pintor et al., 2000; Hervás et al., 2003; Miras-Portugal et al., 2003; Illes and Ribeiro, 2004), which are cloned from various mammalian species (Illes and Ribeiro, 2004). These subunits can occur as homo- or hetero-oligomeric assemblies of more than one subunit (North and Surprenant, 2000), except P2X (Miras-Portugal et al., 2003) receptor, which has been described not to coassemble with other subunits (Torres et al., 1999). They are abundantly expressed in the peripheral and central nervous systems and exhibit high permeability to Ca2+ ions (Cunha and Ribeiro, 2000). The existence of presynaptic ionotropic receptors for nucleotides, either for ATP or dinucleotides, has been reported in isolated synaptic terminals from mammalian brain, and both exhibit good permeability to Ca2+ ions (Pintor et al., 2000; Hervás et al., 2003; Miras-Portugal et al., 2003). Studies on isolated single terminals have confirmed the existence of independent and specific responses to ATP and dinucleotides on the same or different terminals (Miras-Portugal et al., 1999; Díaz-Hernández et al., 2002; Hervás et al., 2005; Sánchez-Nogueiro et al., 2005). The activation of presynaptic ionotropic nucleotide receptors can induce the release of other neurotransmitters such as acetylcholine, glutamate, or GABA. In these specific terminals, ionotropic nucleotide receptors can be modulated by interaction with metabotropic receptors, such as GABAB and adenosine receptors (Khakh and Henderson, 1998; Gómez-Villafuertes et al., 2001), and ionotropic, such as nicotinic cholinergic receptors (Díaz-Hernández et al., 2004; Sánchez-Nogueiro et al., 2005). Here, we discuss a relevant finding on the interaction between ionotropic nucleotide and nicotinic receptors in cholinergic synaptic terminals and the role of CaCMKII in this interaction.

Animals↗
PubMed2005

The ubiquitin-proteasome system in Huntington's disease.

The main histopathological feature of Huntington's disease (HD) is the presence of protein aggregates that are gathered into inclusion bodies. So far the mechanisms that lead to inclusion formation as well as their role in the pathogenesis of HD are not totally understood. However, it is well established that inclusion bodies contain components of the ubiquitin-proteasome system. Accordingly, it has been postulated that impairment of this machinery can be one of the causes of this disorder. In this review, the authors summarize the state of current knowledge about this hypothesis.

Humans↗
PubMed2001

Adenosine triphosphate and diadenosine pentaphosphate induce [Ca(2+)](i) increase in rat basal ganglia aminergic terminals.

Synaptosomal preparations from rat midbrain exhibit specific responses to both ATP and Ap(5)A, which stimulate a [Ca(2+)](i) increase in the presynaptic terminals via specific ionotropic receptors, termed P2X, and diadenosine polyphosphate receptors. Aminergic terminals from rat brain basal ganglia were characterized by immunocolocalization of synaptophysin and the vesicular monoamine transporter VMAT2 and represent 29% of the total. These aminergic terminals respond to ATP and/or Ap(5)A with an increase in the intrasynaptosomal calcium concentration as measured by a microfluorimetric technique. This technique, which allows single synaptic terminals to be studied, showed that roughly 8.2% +/- 1.6% of the aminergic terminals respond to ATP, 16.9% +/- 1.3% respond to Ap(5)A, 32.6% +/- 0.8% to both, and 42.3% +/- 1.5% of them have no response. Immunological studies performed with antibodies against ionotropic ATP receptor subunits showed positive labelling with anti-P2X(3) antibodies in 39% of the terminals. However, colocalization studies of VMAT and P2X(3) receptor subunit indicate that only 25% of the aminergic terminals also contain this receptor subtype. These results demonstrate that the aminergic terminals from the rat brain basal ganglia are to a large extent under the modulation of presynaptic nucleotide and dinucleotide receptors.

Adenosine Triphosphate↗
PubMed2001

Presence of different ATP receptors on rat midbrain single synaptic terminals. Involvement of the P2X(3) subunits.

Adenosine 5'-triphosphate (ATP) stimulates a [Ca(2+)](i) increase via specific ionotropic receptors, termed P2X receptors, in rat midbrain presynaptic terminals. A microfluorimetric technique enabled study of the [Ca(2+)](i) increase in isolated single synaptic terminals, showing that 33.4+/-2.5% of them responded to ATP. Immunological studies carried out, after functional studies, with specific anti-P2X receptor subunit antibodies showed only positive labelling with anti-P2X(3) antibodies in 23.5+/-1.7% of the terminals. All positively P2X(3) labelled synaptic terminals responded to ATP. Nevertheless, not all of them responded to alpha,beta-meATP, these representing 6.7+/-1.5% of the total. In addition, 9.8+/-2.3% of the terminals responded to ATP but exhibit negative P2X(3)-labelling. These results demonstrate the existence of a heterogeneous population of ionotropic ATP receptors at the presynaptic level.

Animals↗
PubMed2001

Independent receptors for diadenosine pentaphosphate and ATP in rat midbrain single synaptic terminals.

Diadenosine pentaphosphate (Ap5A) and adenosine 5'-triphosphate (ATP) stimulate a intrasynaptosomal calcium concentration [Ca(2+)](i) increase via specific purinergic receptors in rat midbrain synaptosomes, although nothing is known about their distribution in presynaptic terminals. A microfluorimetric technique to measure [Ca(2+)](i) increase using the dye FURA-2AM, has permitted study of the presence of dinucleotide and P2X receptors in independent isolated synaptic terminals. Our results demonstrate the existence of three populations of synaptosomes: one with dinucleotide receptors (12%), another with P2X receptors (20%) and a third with both (14%). It has been possible to demonstrate that the activation of these receptors occurs only in the presence of extracellular Ca(2+) and that it is also coupled with voltage-dependent Ca(2+) channels. Finally 54% of the synaptosomes that responded to K(+) did not present any calcium increase mediated by the nucleotides used. In summary, ATP and dinucleotides exhibit specific ionotropic receptors that can coexist or not on the same synaptic terminal.

Animals↗
PubMed2000

Presynaptic signalling mediated by mono- and dinucleotides in the central nervous system.

Synaptosomal preparations from rat midbrain exhibit specific responses to both ATP and Ap(5)A, which elicit a Ca(2+) entrance to the presynaptic terminals. Studies of isolated single terminals showed that not all the terminals contain ionotropic receptors for nucleotides, in fact only 46% of them do. Of these, 12% responded only to the dinucleotide Ap(5)A, and 20% to the mononucleotide ATP. At the presynaptic level, diinosine pentaphosphate, Ip(5)I, is a good tool to specifically block dinucleotide responses, which are inhibited at low nM concentration, versus the high microM concentrations required to block ATP responses. There is evidence for a presynaptic control of mononucleotide and dinucleotide responses, mediated by metabotropic and ionotropic receptors. Stimulation of adenosine A1 receptors increases the affinity of dinucleotide receptors by five orders of magnitude, from 30 microM to 680 pM for control and in the presence of A1 agonist, respectively.

Animals↗
PubMed2000

Modulation of the dinucleotide receptor present in rat midbrain synaptosomes by adenosine and ATP.

Diadenosine polyphosphates activate dinucleotide receptors in rat midbrain synaptic terminals. The agonist with highest affinity at this receptor, diadenosine pentaphosphate (Ap(5)A), elicits Ca(2+) transients at concentrations ranging from 10(-7) to 10(-3) M with a single-phase curve and an EC(50) value of 56.21+/-1.82 microM. Treatment of synaptosomal preparations with alkaline phosphatase (AP) changes the dose-response control curve into a biphasic one presenting two EC(50) values of 6.47+/-1.25 nM and 11.16+/-0.83 microM respectively. The adenosine A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) reversed the biphasic concentration-response for Ap(5)A curve in the presence of AP, to a monophasic one with an EC(50) value of 76.05+/-7.51 microM. The application of adenosine deaminase produced the same effect as DPCPX, the EC(50) value for Ap(5)A, in the presence of AP being 18.62+/-4.03 microM. Activation of the adenosine A(1) receptor by means of cyclohexyladenosine (CHA) shifted the dose response curve for Ap(5)A to the left, resulting in a monophasic curve with an EC(50) of 5. 01+/-0.02 pM. The destruction of extrasynaptosomal nucleotides by AP or the addition of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a broad P2 antagonist compound, enhance maximal effect of the Ap(5)A up to 55.6% on the dose response curve, thus suggesting a negative modulation by P2 receptors. In a summary, ATP and adenosine present at the extra-synaptosomal space, are relevant natural modulators of the dinucleotide receptor, via P2 and adenosine A(1) receptors respectively.

Adenosine↗
PubMed1999

Presence of dinucleotide and ATP receptors in human cerebrocortical synaptic terminals.

Human cerebrocortical synaptic terminals elicited concentration-dependent Ca2+ transients after Ap5A (diadenosine pentaphosphate) and ATP stimulation, with EC50 values of 23.44 +/- 3.70 microM and 11.48 +/- 2.12 microM, respectively. The lack of cross-desensitisation and the selective antagonism by Ip5I (diinosine pentaphosphate), suggests the activation of a dinucleotide receptor by Ap5A, and a P2X receptor by ATP. Ap5A Ca2+ transients were partially abolished by omega-conotoxin GVI-A (53%), suggesting the participation of a N-type Ca2+ channel in the dinucleotide response. ATP effect on Ca2+ entry was abolished by nicardipine (44%) and by omega-conotoxin GVI-A (52%), suggesting the participation of L- and N-type Ca2+ channels. These data suggest that Ap5A and ATP activate dinucleotide and P2X receptors, respectively, in human brain synaptic terminals.

Adenosine Triphosphate↗
PubMedDate not supplied

Diadenosine polyphosphate receptors. from rat and guinea-pig brain to human nervous system.

Diadenosine polyphosphates are a family of naturally occurring nucleotidic compounds present in secretory vesicles together with other chemical messengers. The exocytotic release of these compounds permits them to stimulate receptors termed "purinoceptors" or "ATP receptors." Purinoceptors for nucleotides are named P2 in contrast with those sensitive to nucleosides (P1). P2 receptors are further subdivided into metabotropic P2Y receptors, further divided into 5 subtypes, and ionotropic P2X receptors, with 7 different subtypes. Diadenosine polyphosphates can activate recombinant P2Y(1), P2Y(2), and P2Y(4) and recombinant homomeric P2X(1), P2X(2), P2X(3), P2X(4), and P2X(6). Heteromeric P2X receptors change their sensitivity to diadenosine polyphosphates when co-assembly between different subunits occurs. Diadenosine polyphosphates can activate specific receptors termed dinucleotide receptors or P4 receptors, which are insensitive to other nucleosides or nucleotides. The P4 receptor is a receptor-operated Ca(2)+ channel present in rat brain synaptic terminals, stimulated by diadenosine pentaphosphate and diadenosine tetraphosphate. This receptor is strongly modulated by protein kinases A and C and protein phosphatases. The dinucleotide receptor is present in different brain areas, such as midbrain (in rat and guinea-pig), cerebellum (in guinea-pig), and cortex (in human).

Animals↗