RESUMO
BACKGROUND AND PURPOSE: Dopamine and corticotrophin-releasing hormone (CRH; also known as corticotrophin-releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1 -like dopamine receptors and CRH type-2α receptors (CRF2 α receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2 α receptor. EXPERIMENTAL APPROACH: D1 /CRF2 α receptor heteromerization was demonstrated in HEK293T cells using co-immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co-expressed with CRF2 α receptors, was evaluated by the calcium mobilization assay. KEY RESULTS: D1 /CRF2 α receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2 α receptors accumulated intracellularly. Interestingly, co-expression of both receptors promoted D1 receptor intracellular and CRF2 α receptor cell surface targeting. The heteromerization of D1 /CRF2 α receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist. CONCLUSIONS AND IMPLICATIONS: D1 and CRF2 α receptors are capable of heterodimerization in living cells. D1 /CRF2 α receptor heteromerization might account, at least in part, for the complex physiological interactions established between dopamine and CRH in normal and pathological conditions such as addiction, representing a new potential pharmacological target.
Assuntos
Membrana Celular/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Receptores de Dopamina D1/metabolismo , Cálcio/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Dopamina/metabolismo , Células HEK293 , Humanos , Imunoprecipitação , Transdução de SinaisRESUMO
Song-type switching rate and song matching have been shown to function as territorial signals in male solo song but, to our knowledge, seem not to have been previously studied in a duetting species. We studied the plain wren (Thryothorus modestus zeledoni), to test whether duets signalled threat through song-switching rates, or through phrase type or duet type matching. Increases in the rate of song switching appear to function as an anti-habituation device rather than as a specific signal of threat. Fitting with previous results that same-sex individuals share phrase types, but pairs do not share duet types, both males and females used duets to phrase type match to playback. Pairs, however, did not duet type match in response to playback, and this suggests that within the cooperative territory defence of the duet, each sex is targeting its aggression at same-sex competitors.
Assuntos
Comportamento Cooperativo , Ligação do Par , Aves Canoras/fisiologia , Territorialidade , Vocalização Animal/fisiologia , Estimulação Acústica , Animais , Comportamento Competitivo/fisiologia , Costa Rica , Feminino , Masculino , Espectrografia do Som , Gravação em FitaRESUMO
To determine the calcium and bone mineral status of lactating adolescents, we compared 12 lactating adolescents with 11 nonlactating adolescents, 11 lactating adults, and 11 nulliparous adolescent control subjects. At two and 16 weeks, there were no differences in maternal serum concentrations of calcium, phosphorus, alkaline phosphatase, or calcidiol (25-hydroxyvitamin D). The bone mineral content at two weeks among the four groups was not different, but at 16 weeks the lactating adolescents' bone mineral content was lower than that in the other groups. The lactating adolescents' bone mineral content was decreased between two and 16 weeks (1.049 +/- 0.088 vs 0.887 +/- 0.054 gm/cm; P less than 0.02). Dietary intakes were similar among the groups for calories, protein, vitamin D, calcium, and phosphorus. However, only three of ten lactating adolescents met the recommended dietary allowance for calcium or phosphorus (1,600 mg/day), whereas eight of ten nonlactating adolescents, six of seven lactating adults, and seven of ten adolescents control subjects met the recommended dietary allowance for calcium or phosphorus (P less than 0.05). Our data suggest that during 16 weeks of lactation, the adolescent mother may be at risk for bone demineralization because of low dietary intakes of calcium or phosphorus.