Coupling of receptors in brain membranes by fusion to the adenylate cyclase system of a foreign effector cell.
Receptor-effector coupling in the adenylate cyclase (AC) system was studied using fusion transfer of rat or monkey frontal cortex membranes to Friend erythroleukemia (Fc) cells. The indigenous AC activity of cortex membranes had previously been inactivated with N-ethylmaleimide. In the fusates, the AC activity could be stimulated through beta-adrenoceptors using noradrenaline (NA), or through specific receptors for vasoactive intestinal polypeptide (VIP), or by fluoride which activates the effector components of the AC-system directly, bypassing receptors. There was a critical stoichiometric relationship between the receptor-stimulated cAMP output and the number of recipient cells of the fusion system, i.e. the total AC capacity as measured by fluoride stimulation. In fusates with rat brain membranes, the beta-adrenoceptor coupling increased as the availability of recipient cells increased; on the other hand, the excess of recipient cells did not change the VIP receptor coupling capacity. In fusates with monkey brain membranes, the situation was the opposite: VIP receptor coupling increased as larger amounts of recipient cells were made available, but the beta-adrenoceptor coupling capacity remained unchanged. The differences in coupling capacities were related to differences in receptor binding with higher beta-adrenoceptor density in rat than in monkey frontal cortex membranes, as opposed to higher VIP receptor density in monkey than in rat frontal cortex membranes. Neuropeptide tyrosine (NPY) attenuated both NA- and VIP-induced activation of AC in the fusates; it was equally potent against both agents. In rat brain membrane fusates, the NA-induced AC activity was attenuated in a dose-dependent and apparently non-competitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Olasmaa
M
M
Department of Pharmacology, University of Uppsala, Sweden.
Terenius
L
L
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D005622:Friend murine leukemia virus; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide; D013045:Species Specificity; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D011964:Receptors, Gastrointestinal Hormone; D017981:Receptors, Neurotransmitter; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases; D005459:Fluorides; D009638:Norepinephrine