No abstract

1. The effects of DL-tetrahydropalmatine (DL-THP) on cardio-vascular function and hypothalamic release of monoamines were assessed in rats under urethane anaesthesia. 2. Intravenous administration of DL-THP (1-10 mg/kg) produced hypotension, bradycardia, a decrease in hypothalamic serotonin and noradrenaline release and an increase in hypothalamic dopamine release in rats. 3. Intrahypothalamic administration of DOI (a serotonergic 5-HT2 receptor antagonist) or apomorphine (a dopamine D2-receptor agonist) produced the opposite effects and reversed DL-THP-induced hypotension and bradycardia. 4. The data suggest that DL-THP acts through the 5-HT2 and/or D2-receptor antagonism in the hypothalamus to induce hypotension and bradycardia in rats.

Much evidence shows that glia regulates the cation and anion content of brain interstitial space. In rats the pH and bicarbonate (HCO3-) concentration of neurons and glia were derived from carbon 14-labeled HCO3- and dimethyloxazolidinedione uptake into brain and cerebrospinal fluid. Acetazolamide increases the total CO2 concentration in neurons and decreases the pH and HCO3- concentration in glia. Inhibition of glial carbonic anhydrase (CA) reduces conversion of neuronally derived CO2 to HCO3-, glial pH is lowered, and neuronal CO2 accumulates. CA therefore has an essential role in regulating pH in neurons, glia, and interstitial fluid. In audiogenic seizure mice, glial CA activity is increased and glial anion transport is reduced. As the mice age, seizure susceptibility, the increased CA activity, and the defect in anion transport disappear concurrently. The enhanced CA activity in the glial cells of these mice is an adaptive mechanism to overcome the defect in anion transport that results from a deficiency of HCO3- -dependent and Na+- and K+ -dependent adenosine triphosphatase. Pentylenetetrazol stimulates neurons in neonatal rats, but after 10 days of age, when glia is present, it too is stimulated and the seizures are attenuated. Cobalt implantation in the cortex of rats also induces a glial response that ameliorates the focal seizures produced by this procedure.

Two dwarf brown-egg layer lines, differing in their genotype for the naked neck gene (NA), line L2 (NA*NA/*NA) and line L1 (NA*N/*N), have been selected for 16 generations for increased average clutch length. A control line from the same base population, dwarf and segregating for the NA gene, was maintained by random mating. Genetic parameters were estimated by a multivariate derivative-free restricted maximum likelihood procedure, and the NA gene effect was estimated within the unselected control line. The studied traits included clutch traits, egg production traits, abnormal eggs, egg weight at 36 wk, and BW at 42 wk. The average clutch length, egg number, and maximum clutch length were normalized using the Box-Cox transformation. In response to 16 generations of direct selection for increased average clutch length, other egg production traits, such as laying rate and total egg number, have been indirectly improved in a dwarf layer genetic background. The estimated heritabilities were 0.406 to 0.424 for transformed average clutch length (TCL), 0.373 to 0.411 for transformed egg number (TEN), 0.529 to 0.559 for age at first egg (AFE), 0.275 to 0.282 for laying rate (LR), 0.455 for dutch number (CN), and 0.319 for the number of double-yolked eggs (DYEN). The TCL had high genetic correlations with TEN (0.777), LR (0.863), maximum clutch length (0.902), and CN (-0.845). Selection for increased average clutch length was an effective method for increasing egg production. Line L2 showed a higher egg weight than L1, which indicates that the combined effect of NA and DW genes was favorable to maintain egg weight when egg number could be improved. Line L1 showed a higher number of DYEN, suggesting that the regulation of follicular maturation was changed in this line.

Background and purpose: The study investigated whether eugenosedin-A, a 5-hydroxytryptamine and a/b adrenoceptor antagonist, enhanced delayed-rectifier potassium (K DR )-or large-conductance Ca 2 þ -activated potassium (BK Ca )-channel activity in basilar artery myocytes through cyclic AMP/GMP-dependent and -independent protein kinases. Experimental approach: Cerebral smooth muscle cells (SMCs) were enzymatically dissociated from rat basilar arteries. Conventional whole cell, perforated and inside-out patch-clamp electrophysiology was used to monitor K þ -and Ca 2 þ -channel activities. Key results: Eugenosedin-A (1 mM) did not affect the K DR current but dramatically augmented BK Ca channel activity in a concentration-dependent manner. Increased BK Ca current was abolished by charybdotoxin (ChTX, 0.1 mM) or iberiotoxin (IbTX, 0.1 mM), but not affected by a small-conductance K Ca blocker (apamin, 100 mM). BK Ca current activation by eugenosedin-A was significantly inhibited by an adenylate cyclase inhibitor (SQ 22536, 10 mM), a soluble guanylate cyclase inhibitor (ODQ, 10 mM), competitive antagonists of cAMP and cGMP (Rp-cAMP, 100 mM and Rp-cGMP, 100 mM), and cAMPand cGMP-dependent protein kinase inhibitors (KT5720, 0.3 mM and KT5823, 0.3 mM). Eugenosedin-A reversed the inhibition of BK Ca current induced by the protein kinase C activator, phorbol myristyl acetate (PMA, 0.1 mM). Eugenosedin-A also prevented BK Ca current inhibition induced by adding PMA, KT5720 and KT5823. Moreover, eugenosedin-A reduced the amplitude of voltage-dependent L-type Ca 2 þ current (I Ca,L ), but without modifying the voltage-dependence of the current. Conclusions and implications: Eugenosedin-A enhanced BK Ca currents by stimulating the activity of cyclic nucleotidedependent protein kinases. Physiologically, this activation would result in the closure of voltage-dependent calcium channels and thereby relax cerebral SMCs.