Blocking effect of serotonin on inhibitory dopamine receptor activity of Aplysia ganglion cells.
The abdominal ganglion of Aplysia includes neurons with a characteristic dopamine (DA) receptor, the activation of which induces a marked hyperpolarization with a specific increase in the permeability of the membrane to K+. The DA receptor of this type is called the "HK-type." A 2-min exposure to 1 microM serotonin (5-HT) had little effect on the resting membranes with the receptor of HK-type, but significantly depressed the responses to 10 microM DA. The depressing effect of 5-HT on this type of response was completely reversible after a 15-min washing with normal artificial Aplysia blood. Lineweaver-Burke type plotting of the DA-induced responses showed a systematic shift of the straight lines when the concentration of 5-HT was increased; the slope of the line became steeper but the intercept on the ordinate remained unchanged. The dose-inhibition curves, in which relative responses to a given [DA] were plotted against log [5-HT], showed a parallel shift toward the right when the concentration of DA increased. These findings suggest that 5-HT competes with DA for common binding sites at the DA receptor of HK-type, and that the blockade is not due to the interaction of 5-HT with K+-channels in the receptor membrane. The effect of other indole derivatives suggests that the DA receptor of HK-type includes anionic and cationic sites to which the NH2 group and 5-HO group of 5-HT could specifically bind, thus exhibiting competitive blockade.
D000818:Animals; D001048:Aplysia; D002463:Cell Membrane Permeability / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004874:Ergonovine / Q000494:pharmacology; D005724:Ganglia / Q000166:cytology / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology
D018492:Dopamine Antagonists; D007211:Indoles; D011954:Receptors, Dopamine; D008238:Lysergic Acid Diethylamide; D004298:Dopamine; D004874:Ergonovine