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PubMed1990

Gonadal steroid regulation of substance P (SP) and SP-encoding messenger ribonucleic acids in the rat anterior pituitary and hypothalamus.

Substance P-like immunoreactivity (SP-LI) is present in the rat anterior pituitary (AP) and in hypothalamic neurons that may be involved in the control of AP secretion and/or reproductive function. The presence of multiple SP-encoding mRNAs and tachykinin peptides and their regulation by steroid hormones were examined in APs and hypothalami from normal, gonadectomized, and steroid-treated male and female rats. SP-encoding mRNAs were identified by nuclease protection assays of RNA, and tachykinin peptides were identified by combined HPLC-RIA of tissue extracts, beta- and gamma-preprotachykinin (PPT) mRNAs and SP, neurokinin A, and neuropeptide gamma peptides were identified in the AP. The alpha-, beta-, and gamma-PPT mRNAs and SP, neurokinin A, neuropeptide gamma, neuropeptide K, and neurokinin B peptides were present in hypothalamic tissue. Previous studies have established that in the AP, SP is differentially regulated by gonadal steroids; estrogen decreases and androgen increases AP SP. Steroid effects were further analyzed in experiments using RIAs to measure SP levels in the AP and median eminence (ME) of steroid- and oil-treated gonadectomized rats. To assess whether steroids alter steady state PPT mRNA levels and presumably SP synthesis in these tissues, potential effects on AP and hypothalamic SP-encoding mRNAs were determined. Ovariectomized rats treated for 10 days with estradiol benzoate showed a 50% decrease in AP SP and a 90% decrease in AP beta- and gamma-PPT mRNAs compared to ovariectomized oil-treated controls. Estradiol benzoate replacement had no effect on SP levels in the isolated ME, but did cause a 50% increase in alpha-, beta-, and gamma PPT mRNAs in the hypothalamus. Although there was no significant effect of testosterone propionate on AP SP levels in castrated males, 10 days of testosterone propionate replacement did cause a significant increase in beta- and gamma PPT mRNAs in the AP. No androgen effects were seen on either ME SP or hypothalamic SP-encoding mRNAs. These data demonstrate that estrogen up-regulates SP-encoding mRNAs in the hypothalamus, whereas it down-regulates SP-encoding mRNAs in the pituitary. These results implicate SP and other tachykinins derived from the SP gene as steroid-regulated modulators of AP secretion and possibly reproductive function.

Animals↗
PubMed1995

Hormonal regulation of messenger ribonucleic acid encoding steroidogenic acute regulatory protein in ovine corpora lutea.

Steroidogenic acute regulatory protein (StAR), proposed to be involved in the transport of cholesterol to the inner mitochondrial membrane, has recently been cloned from MA-10 cells. Using reverse transcription-polymerase chain reaction, we generated a complementary DNA encoding 404 base pairs of StAR from ovine luteal tissue to perform studies regarding regulation of the messenger RNA (mRNA) encoding this protein. In Exp 1, ewes were hypophysectomized (HPX) on day 5 of the estrous cycle and administered saline or physiological regimens of LH and/or GH until collection of luteal tissue on day 12 of the estrous cycle (n = 4/group). Luteal concentrations [mean +/- SEM; femtomoles per microgram poly(A)+ RNA] of mRNA encoding StAR were lower (P < 0.05) in the HPX plus saline-treated ewes (26.4 +/- 7.3) than in day 12 pituitary-intact ewes (n = 4; 77.7 +/- 9.3). Replacement of LH (59.1 +/- 13.1), GH (59.1 +/- 12.8), or LH and GH (69.9 +/- 4.5) in HPX ewes increased (P < 0.05) concentrations of mRNA encoding StAR to values not different from those in day 12 controls. In Exp 2, ewes on day 11 or 12 of the estrous cycle were injected with prostaglandin F2 alpha (PGF2 alpha) to induce luteal regression. Corpora lutea were collected 4, 12, or 24 h after injection (n = 4-5/time point) and from untreated control ewes (n = 4) or 24 h after injection of saline (n = 4). Treatment with PGF2 alpha decreased (P < 0.05) concentrations of progesterone in serum 4, 12, and 24 h after injection. Concentrations of StAR mRNA were decreased (P < 0.01) to 47%, 19%, and 8% of control values 4, 12, and 24 h after PGF2 alpha injection, respectively. In Exp 3, ewes received ovarian arterial infusions of saline, PGF2 alpha, or phorbol 12-myristate 13-acetate (PMA), and luteal tissue was collected 0 (no infusion), 4, 12, or 24 h later (n = 3-4/group). Treatment with PGF2 alpha or PMA decreased (P < 0.05) concentrations of progesterone in serum 4, 12, and 24 h postinjection. Steady state concentrations of mRNA encoding StAR (P < 0.05) were 36% and 25% of the control value 12 and 24 h after PGF2 alpha injection. Injection of PMA decreased (P < 0.05) concentrations of StAR mRNA to 75% and 50% of control values at 4 and 12 h, but concentrations of mRNA encoding StAR were not different from control values at 24 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

The role of left-right symmetry in the encodement of spatial orientations.

Three experiments investigated a hypothesis, suggested by studies of the difficulties of discriminating between shapes forming symmetrical pairs, that spatial orientations of thin flat plates (lamellae) may be encoded in a plane, the encodement consisting of two enantiomorphs. The results indicated that participants encoded the spatial orientation of lamellar stimuli in terms of the difference in cogency between their two enantiomorphic elements (Expt 1). The difference in the cogency of the two enantiomorphs is related to the orientation of the plane containing the lamellar stimulus with respect to the participant's fronto-parallel plane (Expt 2). The two possible orientations of a lamella which yield the same difference of cogency, but which differ in spatial orientation (e.g. lamella 'b' set at 30 degrees or set at 150 degrees) are distinguished by the manner in which the two enantiomorphic elements are arranged with respect to their axis of symmetry (Expt 3). The results suggest that the orientation of a lamella may be encoded as a two-dimensional representation and hence that three dimensions may be encoded by two by means of enantiomorphs. Implications of this finding for the encodements of three-dimensional solids, wherein pronounced contours may fulfil the same role as do the edges of lamella, are discussed briefly.

Adult↗
PubMed2005

Imaging systems based on the encoding of optical coherence functions.

An imaging scheme is described that is based on the transmission of image-forming information encoded within optical coherence functions. The scheme makes use of dynamic random-valued encoding-decoding masks placed in the input-output planes of any linear optical system. The mask transmittance functions are complex conjugates of each other, as opposed to a similar coherence encoding scheme proposed earlier by two of this paper's authors that used identical masks. [Rhodes and Welch, in Euro-American Workshop on Optoelectronic Information Processing, SPIE Critical Review Series (SPIE, 1999), Vol. CR74, p. 1]. General analyses of the two coherence encoding schemes are performed by using the more general mutual coherence function as opposed to the mutual intensity function used in the earlier scheme. The capabilities and limitations of both encoding schemes are discussed by using simple examples that combine the encoding-decoding masks with free-space propagation, passage through a four-f system, and a single-lens imaging system.

Journal Article↗
PubMed2005

Retrieval attempts transiently interfere with concurrent encoding of episodic memories but not vice versa.

In the rodent hippocampus, different phases of each theta activity cycle may be devoted to encoding and retrieval processes. These cycles of approximately 3-8 Hz would allow equal processing time for each state and also provide temporal segregation to minimize their mutual interference. We show here that, by controlling the presentation asynchrony between verbal encoding and retrieval cues, theta-resolution (<100 ms) interference-free shifts between functional states are not expressed in hippocampally dependent, human "episodic" memory. Instead, retrieval attempts selectively and transiently interfere, for approximately 450 ms, with the encoding of ongoing experiences. Analyses of scalp event-related potentials confirmed that the functional state of the brain during retrieval is largely unperturbed by concurrent encoding and also suggested that encoding impairments may last until a neocortical phase of retrieval can begin. The findings reveal the dynamic properties of interdependent encoding and retrieval functions that contribute to episodic memory in vivo and, moreover, show that, in humans, this form of memory does not operate with either the equality, or the rapidity, intrinsic to the theta model of rodent hippocampal function.

Adolescent↗
PubMed2006

Differential encoding mechanisms for subsequent associative recognition and free recall.

Recent neuroimaging studies have successfully identified encoding mechanisms that support different forms of subsequent episodic recognition memory. In our everyday lives, however, much of our episodic memory retrieval is accomplished by means of free recall, i.e., retrieval without an external recognition cue. In this study, we used functional magnetic resonance imaging to investigate the encoding mechanisms that support later free recall and their relationship to those that support different forms of later recognition memory. First, in agreement with previous work, we found that activation in the left inferior frontal gyrus and hippocampus correlated with later associative/relational recognition. In these regions, activation was further enhanced for items later freely recalled, pointing to shared underlying relational encoding mechanisms whose magnitude of activation differentiates later successful free recall from successful associative recognition. Critically, we also found evidence for free recall-specific encoding mechanisms that did not, in our paradigm, support later associative recognition compared with item recognition. These free recall-specific effects were observed in left mid/dorsolateral prefrontal (DLPFC) and bilateral posterior parietal cortices (PPC). We speculate that the higher-level working memory operations associated with DLPFC and attention to internal mnemonic representations perhaps mediated via PPC may serve to embed an item into a rich associative network during encoding that facilitates later access to the item. Finally, activation in the perirhinal cortex correlated with successful associative binding regardless of the form of later memory, i.e., recognition or free recall, providing novel evidence for the role of the perirhinal cortex in episodic intra-item encoding.

Adult↗
PubMed2006

Amygdala activity is associated with the successful encoding of item, but not source, information for positive and negative stimuli.

It has been debated whether the link between amygdala activity and subsequent memory is equally strong for positive and negative information. Moreover, it has been unclear whether amygdala activity at encoding corresponds with enhanced memory for all contextual aspects of the presentation of an emotional item, or whether amygdala activity primarily enhances memory for the emotional item itself. In the present functional magnetic resonance imaging study, participants encoded positive and negative stimuli while performing one of two tasks (judgment of animacy or commonness). Amygdala activity at encoding was related to subsequent memory for the positive and negative items but not to subsequent memory for the task performed. Amygdala activity showed no relationship to subsequent-memory performance for the neutral items. Regardless of the emotional content of the items, activity in the entorhinal cortex corresponded with subsequent memory for the item but not with memory for the task performed, whereas hippocampal activity corresponded with subsequent memory for the task performed. These results are the first to demonstrate that the amygdala can be equally engaged during the successful encoding of positive and negative items but that its activity does not facilitate the encoding of all contextual elements present during an encoding episode. The results further suggest that dissociations within the medial temporal lobe sometimes noted for nonemotional information (i.e., activity in the hippocampus proper leading to later memory for context, and activity in the entorhinal cortex leading to later memory for an item but not its context) also hold for emotional information.

Adolescent↗
PubMed1998

Steady-state concentrations of mRNA encoding two inhibitors of protein kinase C in ovine luteal tissue.

Prostaglandin F2 alpha (PGF2 alpha) decreases secretion of progesterone from the corpus luteum in domestic ruminants. However, it is less effective during the early part of the oestrous cycle (Louis et al., 1973) and at the time of maternal recognition of pregnancy (Silvia and Niswender, 1984; Lacroix and Kann, 1986). Decreased luteal responsiveness may be due to failure of PGF2 alpha to activate fully its normal second messenger system, protein kinase C (PKC). Alternatively, increased resistance of the corpus luteum to PGF2 alpha might be attributable to greater concentrations of recently identified biological inhibitors of PKC. These possibilities were addressed by measuring steady-state concentrations of mRNA encoding PGF2 alpha receptor and two inhibitors of PKC, protein kinase C inhibitor-1 (PKCI-1) and kinase C inhibitor protein-1 (KCIP-1, brain 14-3-3 protein), in corpora lutea collected from ewes on days 4, 10 and 15 of the oestrous cycle (n = 5 per day) and day 15 of pregnancy (n = 7). There were no differences in mean concentrations of mRNA encoding PGF2 alpha receptor among the groups. However, concentrations of mRNA encoding both inhibitors of PKC were higher (P < 0.01) on day 4 of the oestrous cycle compared with the other groups. Treatment of ewes with a luteolytic dose of PGF2 alpha, which activates PKC, did not change concentrations of mRNA encoding either PKCI-1 or KCIP-I up to 24 h later. Luteal expression of mRNA encoding the PKC inhibitors and PGF2 alpha receptor was also examined in ewes treated with oestradiol in vivo for 16 h in the midluteal phase. High concentrations of oestradiol in serum (20 and 70 pg ml-1) did not influence quantities of any of the mRNAs examined. Therefore, an increase in PKC inhibitors may be involved in resistance of the corpus luteum to PGF2 alpha during the early part of the oestrous cycle but does not appear to mediate the increased resistance of the corpus luteum to PGF2 alpha during maternal recognition of pregnancy. Neither PGF2 alpha nor oestradiol affected steady-state concentrations of mRNAs encoding PKCI-1 or KCIP-I.

14-3-3 Proteins↗
PubMed1999

Organization and sequences of p-hydroxybenzaldehyde dehydrogenase and other plasmid-encoded genes for early enzymes of the p-cresol degradative pathway in Pseudomonas putida NCIMB 9866 and 9869.

The gene (designated pchA) encoding the aldehyde dehydrogenase that is required to metabolise the p-hydroxybenzaldehyde produced by the degradation of p-cresol in Pseudomonas putida NCIMB 9866 and 9869 has been identified on plasmids pRA4000 and pRA500, respectively. The gene lies immediately upstream of the pchC and pchF genes encoding the subunits of p-cresol methylhydroxylase (PCMH), the preceeding enzyme in the p-cresol degradative pathway. In pRA500 the latter genes are followed by the genes encoding the alpha (pcaG) and beta (pcaH) subunits of protocatechuate-3,4-dioxygenase, whereas in pRA4000 the genes encoding PCMH are followed by an open reading frame encoding a protein that is similar to the maturase-related protein of P. alcaligenes. A gene, designated pchX, that encodes a protein of unknown function was identified between the pchC and pchF genes in both plasmids.

Aldehyde Oxidoreductases↗
PubMed2002

[Encoding genes and genotypes of gamma-lactamases produced by a multiple resistant Klebsiella pneumoniae]

OBJECTIVE: To determine the sequence of gene for encoding beta-lactamase produced by Klebsiella pneumoniae E3 isolated from Jiaxing Area in Zhejiang Province. METHODS The Klebsiella pneumoniae strain E3 was identified as an ESBLs-producing bacterium by inhibitor-potentiated broth dilution test. The gene encoding gamma-lactamase of the strain was amplified by PCR. The purified PCR product was cloned and sequenced by Sanger's dideoxy chain termination composition method. RESULTS The Klebsiella pneumoniae strain E3 produced both TEM and SHV gamma lactamases. The SHV encoding gene had 812 nucleotide residues responsible for encoding SHV-11 gamma-lactamase and the TEM encoding gene had 973 nucleotide residues responsible for encoding TEM-1 gamma-lactamase. CONCLUSION The Klebsiella pneumoniae strain E3 isolated from a patient in Jiaxing Area in Zhejiang Province is able to produce both TEM-1 and SHV-11 gamma-lactamases.

Journal Article↗
PubMed2000

[The influence of verbal encoding on the memory of visual information].

The previous research which investigated the effect of verbal encoding on the memory of visual information has yielded contradictory results: facilitation and inhibition of performance by verbal encoding. However, it has not been elucidated why and how these conflicting results were brought about. The main purpose of this study is to show that verbal encoding not only facilitates but also impairs performance by taking task demand and characteristics of visual representations into account. Another purpose is to investigate how verbal encoding would influence the memory of color information, which is irrelevant for the memory task. In Experiment 1, the results showed that verbal encoding could have two opposite effects in the same task. In Experiment 2, the results showed that the effect of verbal encoding on the memory of color would differ from that on the memory of the shapes of pictures.

Adult↗
PubMed2005

[Effects of contextual variation during encoding on decontextualization of episodic memory].

Two experiments examined whether or not contextual variation during encoding of a list enhances decontextualization of episodic memory of the list. A total of 86 undergraduates incidentally encoded a list of 24 nouns twice under the same (same-context repetition condition) or different (different-context repetition condition) contexts with a one-week inter-encoding interval. One week after the second encoding of the list, the undergraduates were asked to free recall the list under the third neutral context. Context was manipulated by the combination of three contextual elements: physical features of environment, types of encoding tasks, and social factors. Experiment 1 revealed superiority of same-to different-context repetition condition, whereas the preceding studies manipulating only environmental features found superiority of different-to same-context repetition condition. Experiment 2, in which participants were explicitly instructed that the list used in the first and the second encoding sessions were identical, replicated the findings of Experiment 1. The present findings suggest that contextual variation between episodes does not enhance decontextualization of episodic memory.

Adult↗
PubMed2002

Neural correlates of encoding space from route and survey perspectives.

The neural mechanisms underlying ground-level spatial navigation have been investigated, but little is known about other kinds of spatial navigation. Functional magnetic resonance imaging was used to identify differences in brain activation for two types of spatial information, information from the ground-level perspective (route) and information from a global perspective (survey). Participants were scanned during the encoding of two different virtual reality environments, one from each perspective. Comparisons of brain activation during route and survey encoding suggested that both types of information recruited a common network of brain areas, but with important differences. Survey encoding recruited a subset of areas recruited by route encoding, but with greater activation in some areas, including inferior temporal cortex and posterior superior parietal cortex. Route encoding, in contrast, recruited regions that were not activated by survey encoding, including medial temporal lobe structures, anterior superior parietal cortex, and postcentral gyrus. These differences in brain activation are associated with differences in memory performance for the two types of spatial information and contribute to specification of brain components of spatial knowledge.

Adult↗
PubMed2001

HLA-DRB1 alleles encoding an aspartic acid at position 70 protect against development of rheumatoid arthritis.

OBJECTIVE: To determine whether the association between rheumatoid arthritis (RA) and HLA-DRB1 is influenced by the amino acid residue encoded at position 70 (beta70) of the third hypervariable region (HVR3) of the HLA-DRbeta chain. METHODS: The frequencies of HLA-DRB1 alleles encoding different amino acid residues at beta70 were compared between patients with RA and controls in a population from the UK and in a confirmatory population from northwestern Spain. HLA-DRB1 typing was done by polymerase chain reaction methods on 476 clinic based patients with RA and 180 healthy controls from Staffordshire and Cheshire in the UK, and on 179 clinic patients and 145 controls from Lugo, Spain. Associations were investigated using chi-square analyses and regression analyses. The extended Mantel-Haenszel procedure was used for trend analysis. RESULTS: Carriage of 2 shared epitope (SE)+ alleles encoding a glutamine at beta70 (Q70SE+/Q70SE+) was associated with the greatest risk of RA in the UK and Spanish population (odds ratios 7.93 and 4.66, respectively), while possession of 2 SE- alleles encoding an aspartic acid at beta70 (D70SE-D70SE-) was associated with the lowest risk (OR 0.23 and 0.34, respectively). In individuals carrying one SE+ allele and an accompanying D70SE- allele there was no increased risk of developing RA [OR 0.93 (UK) and 1.30 (Spain)]. Possession of D70SE- was more strongly protective than possession of Q70SE. Analysis of trend indicated that the strength of association of different DRB1 genotypes with RA could be ranked in order (from Q70SE+/Q70SE+ to D70SE-/D70SE-) according to which amino acid residues were encoded at beta70, and whether or not they formed part of a SE sequence. The severity of radiographic damage could not be ranked in the same fashion. CONCLUSION: The amino acid residue at position 70 of the HVR3 in HLA-DRbeta molecules influences susceptibility to RA. The strength of the association of DRB1 genotypes with RA is dependent not only on SE status, but also on which amino acid residues are encoded at beta70 of the DRB1 alleles. Presence of an aspartic acid residue at beta70 protects against development of RA. However, the severity of erosive damage does not appear to be associated with the amino acid substitution at 1370.

Alleles↗
PubMed2002

Dissociable human perirhinal, hippocampal, and parahippocampal roles during verbal encoding.

The precise contribution of perirhinal cortex to human episodic memory is uncertain. Human intracranial recordings highlight a role in successful episodic memory encoding, but encoding-related perirhinal activation has not been observed with functional imaging. By adapting functional magnetic resonance imaging scanning parameters to maximize sensitivity to medial temporal lobe activity, we demonstrate that left perirhinal and hippocampal responses during word list encoding are greater for subsequently recalled than forgotten words. Although perirhinal responses predict memory for all words, successful encoding of initial words in a list, demonstrating a primacy effect, is associated with parahippocampal and anterior hippocampal activation. We conclude that perirhinal cortex and hippocampus participate in successful memory encoding. Encoding-related parahippocampal and anterior hippocampal responses for initial, remembered words most likely reflects enhanced attentional orienting to these positionally distinctive items.

Adult↗
PubMed1975

Recognition memory as a function of encoding strategy and stimulus codability.

The primary purpose of this research was to determine how imaginal and verbal encoding strategies intereact with various stimulus characteristics to either enhance or retard recognition; the secondary purpose of these studies was to test the conceptual coding hypothesis of Ellis, 1972. A between-groups multivariate factorial analysis of covariance experiment and a within-subjects multivariate factorial analysis of variance experiment were conducted. In Experiment 1 it was found that low-codability shapes were better recognized under the verbal encoding set rather than the imaginal encoding verbal encoding sets; and high-codability shapes were not better recognized than low-codability shapes. However, in Experiment 2, where instructional set was a within-subjects factor, it was found that low-codability shapes were not better recognized under the verbal encoding set than the imaginal encoding set.

Adult↗
PubMed2003

Recombinant fowlpox viruses encoding the anchor-modified gp100 melanoma antigen can generate antitumor immune responses in patients with metastatic melanoma.

PURPOSE: The purpose of this study was to evaluate the immunological responses and therapeutic effectiveness of immunization with fowlpox vaccines encoding the gp100 melanoma antigen in patients with metastatic melanoma. EXPERIMENTAL DESIGN: In three consecutive clinical trials, patients were immunized with recombinant fowlpox viruses encoding three different forms of the melanoma/melanocyte-associated antigen gp100: (a) the native, full-length gp100 molecule; (b) the gp100 molecule with two amino acids modified to increase binding to HLA-A*0201 molecules; and (c) a "minigene" construct encoding a single, modified epitope gp100:209-217(210M) targeted to the endoplasmic reticulum. The immunogenicity of these constructs was studied using peripheral blood mononuclear cells to measure epitope-specific release of IFN-gamma. RESULTS: Reactivity against gp100 was not seen in any patient before receiving fowlpox immunization. Whereas just one of seven patients developed reactivity after receiving fowlpox encoding native gp100, 10 of 14 patients who received fowlpox encoding the anchor modified full-length gp100 exhibited reactivity against the native gp100 molecule, and 12 of 16 patients were successfully immunized after inoculation with the modified minigene construct (p2 = 0.02). There was no difference in the latter group between those randomized to vaccination by i.v. or i.m. routes. There was one partial cancer regression in the group of 46 patients receiving virus in the absence of interleukin (IL)-2. Once patients showed evidence of progressive disease, they were eligible for "cross-over" treatment to IL-2 alone or with the fowlpox virus. None of the 13 patients receiving the full-length or modified full-length forms of gp100 responded when receiving IL-2, whereas 6 of 12 patients who received the fowlpox containing the minigene construct and then received IL-2 showed objective cancer regressions, including three patients with complete regression. CONCLUSIONS: These data underscore the importance of modifying anchor residues of nonmutated self-antigen peptides to generate cellular immune responses after immunization and support the further investigation of recombinant fowlpox viruses encoding modified epitopes administered in combination with IL-2.

Adult↗
PubMed1992

Class I and IV antiarrhythmic drugs and cytosolic calcium regulate mRNA encoding the sodium channel alpha subunit in rat cardiac muscle.

Previous studies have shown that chronic in vivo treatment with the antiarrhythmic drug mexiletine produces an increase in sodium channel number. We examined whether chronic mexiletine treatment would similarly regulate the level of mRNA encoding the cardiac sodium channel. RNA isolated from cardiac tissue was probed with a 2.5-kilobase cRNA transcribed with T7 RNA polymerase from the clone Na 8.4, which encodes nucleotides 3361-5868 of the alpha subunit of the RIIA sodium channel subtype. Chronic mexiletine treatment produced a 3-fold increase in the level of mRNA encoding sodium channel alpha subunits. Previous studies of cultured skeletal muscle cells had suggested that chronic sodium channel blockade may mediate an increase in sodium channel mRNA by changes in cytosolic Ca2+ concentration. To address this issue, we assessed whether verapamil would also produce up-regulation of the level of mRNA encoding the sodium channel and whether the calcium ionophore A23187 would produce the opposite effect on mRNA level. Verapamil treatment increased sodium channel mRNA level up to 3-fold, whereas in vitro A23187 treatment decreased the mRNA level 5-fold. The combination of verapamil and mexiletine produced no further increase in the mRNA level, compared with that seen with the single agents, suggesting a convergent second messenger pathway for the actions of these two drugs. These data show that the level of mRNA encoding sodium channels is substantially increased during antiarrhythmic drug treatment and suggest that change in cytosolic Ca2+ concentration is the second messenger involved in the regulation of levels of mRNA encoding the alpha subunit of the cardiac sodium channel.

Animals↗