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S M Crain

Publications and source records attributed to S M Crain.

At least 55 records · Page 3Linked to original sources
PubMed1990

Dynorphin prolongs the action potential of mouse sensory ganglion neurons by decreasing a potassium conductance whereas another specific kappa opioid does so by increasing a calcium conductance.

Previous studies have reported that large (microM) concentrations of kappa opioids, e.g. dynorphin and 3,4 dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benzene-acetamide (U-50,488H), shorten the duration of the calcium component of the action potential of dorsal root ganglion neurons by decreasing a voltage-sensitive Ca2+ conductance. The present study showed that, in addition to these inhibitory modulatory effects, small (nM) concentrations of dynorphin, as well as U-50,488H, prolonged the action potential in about 75% of the neurons of dorsal root ganglia in ganglion spinal cord explants of mouse (tested in 5 mM Ba2+). Both the excitatory and inhibitory effects of these kappa opioids were prevented by perfusion together with the opioid antagonist, diprenorphine (10 nM). However, when responsivity tests with opioids were carried out in the presence of multiple K+ channel blockers [Ba2+, Cs+ and tetraethylammonium (TEA)], 1 nM dynorphin prolonged the action potential in only 7% of the neurons (n = 28), whereas 1 nM U-50,488H still elicited the prolongation of the action potential in 60% of the cells (n = 39). These data suggest that dynorphin prolongs the action potential of neurons of dorsal root ganglion by activating a kappa subtype of receptor that decreases a voltage-sensitive K+ conductance, whereas U-50,488H produces similar excitatory modulation of the action potential by activating another kappa subtype of receptor that increases a voltage-sensitive Ca2+ conductance. Thus, U-50,488H-induced prolongation of the action potential appears to be mediated by a kappa subtype of receptor that produces the opposite effect on Ca2+ channels to that which occurs during kappa opioid-induced shortening of the action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Dual opioid modulation of the action potential duration of mouse dorsal root ganglion neurons in culture.

Multiple modulatory effects of opioids on the duration of the calcium component of the action potential (APD) of dorsal-root ganglion (DRG) neurons of mouse spinal cord-ganglion explants were studied. The APD of DRG neuron perikarya has been previously shown to be shortened by exposure to high concentrations of opioids (ca. 0.1-1 microM) in about 1/2 of the cells tested. The present study demonstrates that in addition to these inhibitory modulatory effects of opioids, lower concentrations (1-10 nM) of present study demonstrates that in addition to these inhibitory modulatory effects of opioids, lower concentration (1-10 nM) of delta- mu, and kappa-opioid agonists elicit excitatory modulatory effects, i.e. prolongation of the APD, in about 2/3 of the sensory neurons tested. APD prolongation as well as shortening elicited by delta, mu, and kappa agonists were prevented by coperfusion with the opioid antagonists, naloxone or diprenorphine (10 nM). APD prolongation induced by the delta-agonist [D-Ala2-D-Leu5]enkephalin (DADLE) was prevented in the presence of multiple K+ channel blockers, whereas excitatory modulation by the specific kappa-agonist, U-50,488H was not attenuated under these conditions. After treatment of DRG neurons with pertussis toxin (1 micrograms/ml for several days) or forskolin (50 muM for less than 15 min), a much smaller fraction of cells showed opioid-induced APD shortening; moreover, a much larger fraction of cells showed opioid-induced APD prolongation, even when tested with high concentrations of DADLE (1-10 muM). These data indicate that opioid-induced APD prolongation is not mediated by pertussis toxin-sensitive G proteins (which have been shown to regulate opioid inhibitory effects) and suggest that elevation of cyclic AMP levels may enhance opioid excitatory responsiveness. Furthermore, our analyses indicate that mu-, delta- and kappa-subtypes of excitatory as well as inhibitory opioid receptors may be expressed on the same DRG neuron perikaryon under in vitro conditions. If dual opioid modulation of the APD of DRG perikarya also occurs in central DRG terminals this may play a significant role both in nociceptive signal transmission as well as tolerance to opioid analgesia.

Action Potentials↗
PubMed1989

Embryonic spinal cord neurons develop preferential cholinergic projections to sympathetic ganglia explanted from appropriate levels of the neuraxis.

To determine whether cholinergic spinal cord neurons can develop preferential projections in vitro within sympathetic ganglia (SGs) of appropriate levels of the neuraxis, organotypic explants of fetal mouse spinal cord (E13) from cervical, thoracic (upper and lower) and lumbar segments were co-cultured with either pairs of neonatal SGs: the rostral superior cervical ganglion (SCG) or a caudally located upper lumbar ganglion (LG). After 3.5-4 weeks of co-culture, levels of the enzyme, choline acetyltransferase (ChAT), were measured in individual spinal cord explants and SCGs or double LGs (to match the target mass of a single SCG). Interaction was assumed to occur primarily between an SCG or LG doublet and the adjacent ipsilateral half of the co-cultured cord segment. An index of cholinergic interaction was defined as the ganglion ChAT activity per unit ChAT activity in half co-cultured cord segment. The index of interaction with the SCG was highest with the T1/T2 (1.4) as compared with the T10/T11 (0.79), L1/L2 (0.38) and C2/C3 (0.11) segments. In contrast, the index of cholinergic interaction with double LGs was highest with the more caudally located T10/T11 (0.62) cord segment as compared with the rostral T1/T2 (0.33), cervical C2/C3 (0.2) and lumbar L1/L2 (0.17) segments. Ganglion compound action potentials evoked in LGs by stimulation of the ipsilateral portion of T10/T11 cord were blocked by the ganglionic antagonist, hexamethonium, as previously observed in co-cultures of SCGs with T1/T2 cord. These results indicate that pools of preganglionic neurons in thoracic cord segments can develop in vitro preferential cholinergic projections within SGs of appropriate position. Cervical and lumbar cord segments which contain a preponderance of somatic motoneurons over preganglionic neurons did not interact as effectively with either type of SG. The preferential cholinergic projections from rostral thoracic cord explants within co-cultured SCGs and from caudal thoracic cord explants within co-cultured SCGs and from caudal thoracic cord explants within LGs may reflect some degree of positional preference intrinsic to embryonic spinal cord neurons and/or their appropriate target SGs, consistent with the positional specificity expressed by preganglionic neurons and SGs in situ.

Action Potentials↗
PubMed1988

Inhibitor of cyclic AMP-dependent protein kinase blocks opioid-induced prolongation of the action potential of mouse sensory ganglion neurons in dissociated cell cultures.

The duration of the calcium component of the action potential (APD) of dorsal root ganglion (DRG) neurons in mouse spinal cord-ganglion explants has been shown to be dually modulated via excitatory and inhibitory opioid receptors. In order to determine if opioid-induced APD prolongation is modulated by receptors that are positively coupled to the adenylate cyclase (AC)/cyclic AMP second messenger system, whole-cell recordings were made from mouse DRG neurons grown in dissociated cell cultures. Tests for opioid responsivity were carried out after intracellular dialysis of an inhibitor of cAMP-dependent protein kinase (PKI). In control recordings, both DADLE-induced APD prolongation as well as shortening were prevented by co-perfusion with the opioid antagonist, diprenorphine (10 nM). Intracellular dialysis of PKI in these neurons completely blocked opioid-induced APD prolongation but did not attenuate APD shortening generally elicited by higher opioid concentrations. Bath perfusion of 10 nM DADLE elicited APD prolongation in 59% of the DRG neurons (n = 34) tested with control solution in the recording pipette, whereas none showed APD prolongation when the pipette contained PKI (n = 18). In control tests with 1 microM DADLE, the APD was prolonged in 37% of the cells and shortened in 26% (n = 19); in contrast, a matched group of PKI-treated cells showed no APD prolongation, whereas 42% showed APD shortening (n = 26). The results support the hypothesis that opioid-induced APD prolongation in DRG neurons is mediated by opioid receptor subtypes that are positively coupled via Gs to AC/cAMP-dependent voltage-sensitive ionic conductances.

Action Potentials↗
PubMed1988

Preferential cholinergic projections by embryonic spinal cord neurons within cocultured mouse superior cervical ganglia.

The development of preferential cholinergic projections of spinal cord neurons within superior cervical ganglia (SCG) was analyzed in vitro using cocultures of SCGs (E17) with organotypic explants of fetal mouse cord (E13). The cord explants consisted of: (1) dorsal vs medioventral strips or mediodorsal vs ventral strips (dissected from levels C8-T4), or (2) transverse sections cut at various levels of the neuraxis. After 4 weeks of coculture, choline acetyltransferase (ChAT) was assayed in individual explants to quantify development of the cholinergic neurotransmitter enzyme (a) within the cord neurons, and (b) within the SCG. An index of cholinergic interaction was calculated as the relative ChAT activity in cocultured ganglion per unit ChAT activity in the ipsilateral cord strip. The highest index value (0.7) was obtained in cocultures with mediodorsal strips of cord. The index of interaction was progressively lower with medioventral (0.4), ventral (0.3) and dorsal (0.1) cord. In cocultures of transverse sections of spinal cord and SCGs, the highest indices of cholinergic interaction (expressed per hemisection of cord) were obtained with cord levels T1/T2 (1.0) and T5 (0.9). The index decreased with T9 (0.7) and was significantly lower with segments C2/C3 (0.3) and L2/L3 (0.19). Addition of a skeletal muscle target explant to the cord-SCG cocultures did not alter the preferential index of interaction between SCG and upper thoracic cord levels. Furthermore, the cholinergic cord neurons in medioventral strips did not promote increase of ChAT activity into equally accessible cocultured ganglia of inappropriate phenotype, e.g. sensory dorsal root ganglia. Decentralization of SCGs after coculture with appropriate T1/T2 cord resulted in loss of ganglionic ChAT activity. Electrical stimulation of the medial region in T1/T2 cord explants evoked compound ganglion action potentials in cocultured SCGs. The ganglion responses were blocked by hexamethonium. These data suggested that neurons located in the medial region of upper thoracic cord (presumably autonomic preganglionic) are able to develop enhanced cholinergic projections within cocultured SCGs, in comparison with neurons located in ventral cord (presumably motoneurons). In contrast, dorsal cord neurons showed no significant cholinergic interaction with SCGs. Furthermore, neurons located in upper thoracic spinal cord segments develop enhanced cholinergic projections within cocultured SCGs in comparison with neurons located in cervical and lumbar cord segments.

Acetylcholine↗
PubMed1988

Opioids excite rather than inhibit sensory neurons after chronic opioid exposure of spinal cord-ganglion cultures.

Tests were carried out to determine if the tolerance that develops in dorsal-horn network responses of mouse dorsal root ganglion (DRG)-spinal cord explants after chronic exposure to opioids could be accounted for by alterations in the excitability and pharmacologic properties of the afferent DRG cells. Intracellular recordings were made from DRG neurons in organotypic DRG-cord explants after chronic treatment with 1 microM D-Ala2-D-Leu5-enkephalin (DADLE) for greater than 4 days in vitro. Acute application of 10 microM DADLE shortened the duration of the Ca2+ component of the somatic action potential (APD) in only 5% of the treated neurons (4 out of 79 cells), in contrast to about 50% of the cells in naive explants (36 out of 74). Thus many DRG neuron perikarya became tolerant to the APD-shortening effects of DADLE. Furthermore, 77% of the treated DRG cells (61 out of 79) showed prolongation of the APD in response to an acute increase in DADLE concentration vs 34% in naive explants (25 out of 74). However, when the DADLE responsivity tests were carried out in the presence of multiple K+ channel blockers, only 20% of the treated DRG neurons showed APD prolongation (3 out of 15 cells), whereas 73% showed APD-shortening responses (11 out of 15 cells). The results suggest that: (1) DADLE-induced APD prolongation of the treated DRG neurons is mediated by opioid receptor subtypes that decrease a voltage-sensitive K+ conductance; (2) the DADLE-induced APD-shortening effects which are unmasked during more complete K+ channel blockade are mediated by opioid-receptor subtypes in the same neuron that reduce a voltage-sensitive Ca2+ conductance (resembling kappa receptors). DRG neurons did not become tolerant to either of these two opioid effects after chronic exposure to DADLE. Opioid shortening of the APD of DRG neuron perikarya has been generally accepted to be a model of opioid inhibition of calcium influx and transmitter release at presynaptic DRG terminals6,52,53,65,75,76. It is postulated that the opioid-induced APD prolongation observed in the present study provides evidence that opioids can also evoke direct excitatory effects on neurons. The enhancement of DADLE-induced excitatory responses and attenuation of DADLE-induced inhibitory responses of DRG neurons after chronic exposure to this opioid show striking similarities to the effects of forskolin or pertussis toxin treatment. These in vitro studies may provide clues to compensatory mechanisms underlying physiologic expression of tolerance to opioid analgesic effects in primary afferent synaptic networks.

Action Potentials↗
PubMed1988

Modulation of adenylate cyclase activity of mouse spinal cord-ganglion explants by opioids, serotonin and pertussis toxin.

Organotypic cultures of fetal mouse spinal cord-ganglion explants (2-4 weeks in vitro) contain forskolin-stimulated adenylate cyclase (AC) activity that is inhibited by levorphanol and other opioid agonists in a dose-dependent manner. Inhibition by levorphanol no longer occurs if sodium is omitted from the incubation and the levorphanol inhibition is blocked by the opioid antagonist, naloxone. These findings together with the ineffectiveness of dextrorphan indicate that the opioid inhibition of forskolin-stimulated AC is receptor mediated. Both the delta- and kappa-receptor subtypes appear to be involved since the selective delta-opioid agonist, [D-Pen2, D-Pen5]enkephalin, and the selective kappa-opioid agonist, t-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)cyclohexyl]-benzene acetamide (U-50,488H) are both effective at nanomolar concentrations. In contrast, the selective mu-opioid agonist, Tyr-D-Ala-Gly-N-MePhe-Gly-ol, has no significant effect even at micromolar concentrations. Both cord and ganglion components of the explants contain opioid-sensitive AC. Forskolin-stimulated AC of the explants is also inhibited by serotonin and carbachol. The serotonin effect appears to be mediated by 5-HT1A receptors, based on relative agonist and antagonist selectivity. Chronic exposure of cultures to morphine results in enhanced basal and forskolin-stimulated AC as well as attenuation of opioid-inhibition of AC assayed in the presence of forskolin; treatment of explants with pertussis toxin causes similar changes in the AC system. The inhibitory effect of serotonin is also attenuated by the pertussis toxin treatment. Basal AC activity of the explants (assayed without forskolin present) is stimulated to a small but significant extent by opioids and by serotonin. The opioid stimulatory effect is markedly enhanced following either morphine or pertussis toxin treatment of the explants. The attenuation of opioid- and serotonin-inhibition of AC produced by chronic exposure to pertussis toxin and the attenuation of opioid inhibition produced by exposure to morphine are consonant with the attenuation of opioid and monoaminergic depression of sensory evoked dorsal horn network responses after similar chronic treatments. It is proposed that the inhibitory effects of opioids and serotonin on these neurons are mediated by receptors that are negatively coupled via a pertussis toxin sensitive Gi protein to AC. Furthermore, alterations of AC with chronic morphine treatment may be involved in the development of physiologic tolerance to opioids.

Adenylate Cyclase Toxin↗
PubMed1987

Pertussis toxin blocks depressant effects of opioid, monoaminergic and muscarinic agonists on dorsal-horn network responses in spinal cord-ganglion cultures.

After chronic exposure of mouse spinal cord-ganglion explants to morphine, the acute depressant effects of opioids on sensory-evoked dorsal-horn network responses are markedly attenuated, and characteristic cord discharges can then occur even in the presence of greater than 100-fold higher opioid concentrations. The present study demonstrates that a remarkably similar degree of tolerance to opioids develops in these cord-ganglion explants after exposure to pertussis toxin (PTX). The usual acute depressant effects of serotonin, norepinephrine and oxotremorine on dorsal-horn discharges are also similarly attenuated in PTX-treated cultures. PTX is known to interfere with the guanine nucleotide protein Gi that is required for opioid, alpha 2-adrenergic and muscarinic receptor-mediated inhibition of adenylate cyclase in various cells. We have previously found that in cord-dorsal root ganglion explants agents which elevate intracellular cAMP also attenuate opioid depressant effects. Furthermore, these explants contain an opioid-inhibited adenylate cyclase system, and chronic exposure to morphine as well as PTX increases adenylate cyclase activity. These findings together with the present results suggest that the neuromodulatory effects of opioid, monoaminergic and muscarinic agonists on primary afferent networks in the spinal cord may be mediated by binding to neuronal receptor subtypes that are negatively coupled via Gi to a common pool of adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1987

Nerve growth factor regulates the action potential duration of mature sensory neurons.

The effect of nerve growth factor (NGF) on the action potential of sensory ganglion neurons was investigated in long-term organotypic cultures of embryonic mouse dorsal root ganglia grown isolated or attached to spinal cord explants. The present study demonstrates that NGF regulates a specific bioelectric property of these neurons--the duration of the Ca2+ component of the somatic action potential--at mature stages when they no longer require NGF for survival. Prolonged culture of fetal mouse dorsal root ganglion neurons with relatively low levels of NGF shortens the duration of the action potential. Furthermore, addition or withdrawal of NGF in mature cultures results, within several days, in shorter or longer action potential durations, respectively. Exposure to anti-NGF antiserum accelerates the onset of the longer-lasting action potentials elicited by simple withdrawal of NGF. This plastic response of sensory neurons to NGF may be important in regulating their physiological properties and/or their response to injury.

Action Potentials↗
PubMed1986

Sustained hyperexcitability elicited by repetitive electric stimulation of organotypic hippocampal explants.

Sustained or complex evoked extracellular slow-wave field potentials were recorded in the CA3/2 areas of organotypic hippocampal explants following stimulation of the dentate area. After repetitive electric stimulation, these discharges became more complex and/or self-sustaining. Self-sustaining discharges continued to occur for the duration of the experiment (15 min-10 h). These slow-wave discharges were evoked (or occurred spontaneously) over a wide range of extracellular K+ concentrations (3-9 mM) without addition of pharmacologic inhibitory antagonists, whereas in some explants raising extracellular K+ from 5.9 to 8-9 mM resulted in spontaneous discharges. The observation that epileptiform discharges in hippocampal explants often occurred spontaneously, were elicited by repetitive electric stimulation, and were recorded at K+ levels which are generally ineffective in acute adult hippocampal slices, indicates that excitability of these CNS explants may be significantly increased following altered neuronal and synaptic development (and/or reorganization) under isolated conditions in culture.

Animals↗
PubMed1986

Cyclic AMP or forskolin rapidly attenuates the depressant effects of opioids on sensory-evoked dorsal-horn responses in mouse spinal cord-ganglion explants.

Exposure of fetal mouse spinal cord-ganglion explants to morphine (greater than 0.1 microM) results in naloxone-reversible, dose-dependent depression of sensory-evoked dorsal-horn synaptic-network responses within a few minutes. After chronic opiate exposure (1 microM) for 2-3 days, these dorsal cord responses recover and can then occur even in greater than 10 microM morphine. In the present study, when naive explants were treated with forskolin (10-50 microM)--a selective activate activator of cyclase (AC)--for 10-30 min prior to and during exposure to morphine (0.1-0.3 microM) or D-Ala2-D-Leu5-enkephalin (0.03-0.1 microM), the usual opioid depressant effects on dorsal-horn responses generally failed to occur (10-30 min tests). Dibutyryl cyclic AMP (10 microM) or the more lipid-soluble analog, dioctanoyl cyclic AMP (0.1 mM), produced a similar degree of subsensitivity to opiates as 10 microM forskolin. With high levels of forskolin (50 microM), even concentrations of morphine up to 1-10 microM were far less effective in depressing cord responses. These effects of exogenous cAMP analogs and forskolin on cord-ganglion explants are probably both mediated by increases in intracellular cAMP. The marked decrease in opioid sensitivity of cAMP or forskolin-treated cord-ganglion explants provides significant electrophysiologic data compatible with the hypothesis that neurons may develop tolerance and/or dependence during chronic opioid exposure by a compensatory enhancement of their AC/cAMP system following initial opioid depression of AC activity. Previous evidence relied primarily on behavioral tests and biochemical analyses of cell cultures. It will be of interest to determine if dorsal-horn tissues of cord-ganglion explants do, in fact, develop increased AC/cAMP levels as they express physiologic signs of tolerance during chronic exposure to opioids.

Animals↗
PubMed1986

Dendritic patterns of granule cells in organotypic explants of fetal and neonatal mouse hippocampal formation.

Granule and granule-like neurons were labeled by Golgi and HRP techniques in the dentate area of fetal and neonatal organotypic hippocampal explants after 1 day-8 weeks in vitro. These cells resembled granule cells labeled in situ with similar techniques, although the dendritic pattern and spine development were not as elaborate as observed on granule cells from adult rodents. Many of these neurons retained basilar or multiple dendrites after 8 weeks in culture, a characteristic often associated with immature granule cells, granule cells in the reeler mutant mouse and tissues removed from human epileptic foci.

Animals↗
PubMed1986

Maturation of opioid sensitivity of fetal mouse dorsal root ganglion neuron perikarya in organotypic cultures: regulation by spinal cord.

Opioid agonists selectively decrease the duration of the Ca2+ component of the action potential recorded from embryonic dorsal root ganglion neurons in dissociated cell cultures. In contrast, no significant alterations in the action potentials generated by adult dorsal root ganglion neurons in vivo were detected during opioid exposure. In the present study, the perikaryal opioid sensitivity of fetal mouse dorsal root ganglion neurons was analyzed during maturation in organotypic explant cultures. To determine whether spinal cord might influence this sensitivity, neuron perikarya were tested in ganglia grown: (a) in isolation; (b) attached to spinal cord explants; and (c) attached to spinal cord, but decentralized by a dorsal root transection in mature explants 1-2 weeks before the tests. After 2-8 weeks in culture, the duration of the Ba2+-enhanced Ca2+ component of intracellularly recorded action potentials was measured prior to and during bath exposure to the opioid, [D-Ala2, D-Leu5]enkephalin. Sensitive neurons were characterized by a marked, reversible reduction (averaging about 50%) in the duration of the Ca2+ component (which was antagonized by naloxone). The fraction of opioid-sensitive neuron perikarya in dorsal root ganglia grown attached to cord explants was significantly lower (48%) than in ganglia grown isolated (78%) or decentralized in vitro (79%). The mean duration of the Ca2+ component was significantly shorter in ganglion cells which had been grown attached to cord, or subsequently decentralized, compared to cells grown in isolated ganglia (by 24 and 38%, respectively). This difference was even larger in the opioid-insensitive groups. Although opioid-sensitive perikarya in ganglia grown attached to cord had a significantly longer Ba2+-enhanced Ca2+ component than that of insensitive neurons, some of the insensitive perikarya in all 3 types of explant paradigms displayed Ca2+ components which were as prolonged as those of sensitive cells. The results obtained in this study support the hypothesis that the observed decrease in the fraction of opioid-sensitive perikarya during development of fetal mouse dorsal root ganglia is due to regulation by interactions with their central target tissue, the spinal cord. The developmental decrease in the duration of the Ca2+ component of the action potential of these ganglion cells is also enhanced by the presence of the spinal cord. However, regulation of functional opiate receptors and Ca2+ component duration of the ganglion cell perikarya appear to be independent processes.

Action Potentials↗
PubMed1986

Antagonist-induced opiate receptor upregulation in cultures of fetal mouse spinal cord-ganglion explants.

Chronic exposure of fetal mouse spinal cord-ganglion explants to the opioid antagonist naloxone (10 microM, 7 days) produced a pronounced upregulation of mu opioid receptors. The antagonist action was stereospecific, as it was produced by (-)-, but not by (+)-naloxone, and was dose-dependent. Half-maximal naloxone-induced receptor upregulation occurred after two days; receptor density was maximal at 5 days. Exposure of the explant cultures to naloxone (10 microM) in the presence of the protein synthesis inhibitor, cycloheximide (1 microM; a concentration which blocks greater than 90% protein synthesis) resulted in receptor density changes that were similar to those observed in cultures exposed to naloxone alone. This finding suggests that antagonist-induced opiate receptor upregulation does not require the synthesis of new receptor molecules.

Animals↗
PubMed1986

Pertussis toxin treatment results in tolerance to the depressant effects of opioid, monoaminergic, and muscarinic agonists on dorsal-horn network responses in mouse spinal cord-ganglion cultures.

After treatment of mouse spinal cord-ganglion explants with pertussis toxin (PTX), the acute depressant effects of opioids on sensory-evoked dorsal-horn network responses are markedly attenuated, and characteristic cord discharges can then occur even in the presence of greater than 100-fold higher opioid concentrations, as observed after chronic exposure to opioids. The usual acute depressant effects of serotonin, norepinephrine, and oxotremorine on dorsal-horn discharges are similarly attenuated in PTX-treated cultures. These results together with our previous physiologic and biochemical analyses of adenylate cyclase (AC) and cyclic AMP (cAMP) activities in cord-ganglion cultures suggest that the neuromodulatory effects of opioid, monoaminergic and muscarinic agonists on primary afferent networks in the spinal cord may be mediated by binding to neuronal receptor subtypes that are negatively coupled via Gi to a common pool of AC.

Adenylate Cyclase Toxin↗
PubMed1985

Systemic pseudallescheriasis in a patient with acute myelocytic leukemia.

Presented is a case of widely disseminated systemic pseudallescheriasis in a 41 year old male with acute myelocytic leukemia. The immediate cause of death appeared to be due to an extensive invasion of the lungs which showed massive intra-alveolar hemorrhages, congestion, mycotic thrombi, and multiple fungal lesions in all lobes. Pseudallescheria boydii was diagnosed histopathologically by virtue of its characteristic conidia present in miliary lesions throughout a wide range of host's tissues, including the brain and the thyroid. Three antemortem blood specimens cultured during the patient's final hospital stay were positive for the fungus. It was concluded the fungemia was responsible for the rapid and widespread dispersion of P. boydii in this debilitated patient who was granulocytopenic and immunosuppressed.

Adult↗