Both GABA A and GABA B receptors participate in suppression of [Ca 2+] i pulsing in toad melanotrophs

Abstract

The receptor mechanisms involved in the inhibitory effect of γ-aminobutyric acid (GABA) in suppressing spontaneous [Ca 2+] i pulsing in melanotrophs of Xenopus laevis were investigated. The selective GABA B receptor agonist, baclofen reversibly arrested [Ca 2+] i pulsing. This inhibition was unaffected by the selective GABA A receptor antagonist, bicuculline methiodide, but was blocked by the selective GABA B receptor antagonist, CGP 35348 (3-aminopropyl diethyoxymethyl phosphinic acid). The selective GABA A receptor agonist, muscimol, also arrested [Ca 2+] i pulsing after causing a transient rise in [Ca 2+] i. This biphasic response to muscimol was unaffected by CGP 35348, but was blocked by bicuculline. The inhibitory effect of GABA was unaffected by either CGP 35348 or bicuculline when given alone, but was blocked by both antagonists given together. In cells pretreated with pertussis toxin, the response to baclofen was completely lost, whereas responses to GABA and muscimol persisted; the response to GABA was blocked by bicuculline alone. Thus, both GABA A and GABA B receptors are involved in the inhibitory effect of GABA in suppressing spontaneous [Ca 2+] i pulsing in Xenopus melanotrophs.