α₂‐Adrenergic, k‐Opiaie, and P_rPurinergic Autoreceptors Have Mutually Antagonistic Effects: A New Regulatory Mechanism?

Abstract

Rat cortical synaptosomes prepared on four-step discontinuous Percoll density gradients were loaded with the fluorescent Ca2+-indicator fura-2 to allow measurement of the intrasynaptosomal free calcium concentration ([Ca2+]i). When P1-purinergic, alpha 2-adrenergic, or kappa-opiate agonists were incubated with these synaptosomes for 1 min, there was a highly significant, dose-dependent reduction in [Ca2+]i. The effects of these agonists were blocked by inclusion of appropriate specific antagonists. When alpha 2-adrenergic and P1-purinergic agonists were coincubated, a mutual antagonism of their effects was observed, and, in fact, an increase rather than a decrease in [Ca2+]i was apparent. This mutual antagonism was reversed by addition of either a P1-purinergic or a alpha 2-adrenergic antagonist. Parallel studies in which kappa-opiate and P1-purinergic agonists were coincubated also demonstrated a mutual antagonism between the individual effects that was reversed by prior inclusion of either a kappa-opiate or P1-purinergic antagonist. As these mutually antagonistic effects have been observed between alpha 2-adrenergic, kappa-opiate, and P1-purinergic receptor-mediated events, we suggest that this may be a general phenomenon and may be a regulatory mechanism at nerve endings.

Kappa-opioid ligands in the study and treatment of mood disorders

“…They affect other neurotransmitter systems that may be important in regulating mood. Indeed, NE release is reduced by KOR agonists, as studied in rat synaptosomes (Adamson et al, 1989) and rabbit hippocampal slices (Allgaier et al, 1989). In addition, the effects of KOR agonists on monoamine turnover may differ by brain region (Ford et al, 2006).…”

Direct effect of adenosine on prolactin secretion at the level of the single rat lactotroph: involvement of pertussis toxin-sensitive and -insensitive transducing mechanisms

“…Since PTX pretreatment completely abolishes the inhibition by adenosine of prolactin secretion and inositol phosphate produc¬ tion, our data strongly support the direct coupling of the Al receptor with phospholipase C via a PTX-sensitive G protein, and the involvement of this receptor in the control of prolactin secretion. Although adenosine has been shown to inhibit inositol phosphate production, its involvement in the control of calcium homeostasis has been mainly ascribed to the purine inhibitory effect on calcium currents in different tissues Adamson et al 1989;Kirsch et al 1991;Scholz & Miller, 1991). As far as the effect of adenosine on TRH-induced changes in [Ca +]¡ in GH3 cells is concerned, Cooper et al (1989) reported an inhibitory action of phenylisopropyl adenosine only on the second phase of the calcium elevation evoked by TRH, which is known to be dependent on the influx of extracellular calcium.…”

Control of glutamate release by calcium channels and κ‐opioid receptors in rodent and primate striatum

“…A number of mechanisms have been suggested to modulate this inhibition. These include, inhibition (or reduced activation) of voltagedependent Ca 2+ -channels (VDCCs) (Cherubini & North, 1985;Gross & McDonald, 1987;Adamson et al, 1989;Xiang et al, 1990;Wiley et al, 1997), activation of a K + conductance (Shen & Crain, 1990;Grudt & Williams, 1993;Ma et al, 1995;Henry et al, 1995;Ikeda et al, 1995) and inhibition of Na + -channels (Millan et al, 1995). The inhibition of Ca 2+ -channels by kopioid-receptor activation is thought to be G-protein-mediated (Gross & Macdonald, 1987;Rhim & Miller, 1994;Wiley et al, 1997).…”