Pachter J A, Lam D M
J Neurochem. 1986 Jan;46(1):257-64. doi: 10.1111/j.1471-4159.1986.tb12955.x.
Although 3,4-dihydroxyphenylethylamine (dopamine, DA) and vasoactive intestinal peptide (VIP) have been reported to stimulate adenylate cyclase activity in the rabbit retina, possible interactions between VIP-sensitive and DA-sensitive adenylate cyclase systems have not been previously investigated. To elucidate the interactions between these two putative transmitter-stimulated cyclase systems, the effects of VIP, DA, and VIP + DA on the conversion of [alpha-32P]ATP to [32P]cyclic AMP in rabbit retinal homogenates were measured. VIP stimulated adenylate cyclase activity in a biphasic manner, suggesting that two classes of VIP receptors may be involved in the induction of cyclic AMP formation. DA was less potent than VIP, and stimulated cyclase activity with a monophasic dose-response curve. When assayed together, these stimulations were partially nonadditive, implying the existence of a common adenylate cyclase pool that may be stimulated by both putative neurotransmitters. The dopaminergic antagonist (+)-butaclamol completely blocked dopaminergic stimulation, but had no significant effect on VIP-induced stimulation, indicating that VIP interacts with specific VIP receptor sites, which are distinct from the dopaminergic receptor sites. Furthermore, the specific D-2 dopaminergic receptor agonist LY141865 demonstrated no inhibitory effect on adenylate cyclase activity, suggesting that the interaction between the VIP- and DA-sensitive adenylate cyclase systems does not result from a D-2 receptor-mediated cyclase inhibition in the rabbit retina. Finally, at maximally effective concentrations, DA and VIP were less potent than fluoride or forskolin in the stimulation of cyclic AMP formation, suggesting that adenylate cyclase pools that are not sensitive to DA and VIP may also be present in this retina.(ABSTRACT TRUNCATED AT 250 WORDS)
尽管据报道3,4-二羟基苯乙胺(多巴胺,DA)和血管活性肠肽(VIP)可刺激兔视网膜中的腺苷酸环化酶活性,但VIP敏感和DA敏感的腺苷酸环化酶系统之间可能的相互作用此前尚未得到研究。为了阐明这两种假定的递质刺激的环化酶系统之间的相互作用,测定了VIP、DA以及VIP + DA对兔视网膜匀浆中[α-32P]ATP转化为[32P]环磷酸腺苷的影响。VIP以双相方式刺激腺苷酸环化酶活性,这表明两类VIP受体可能参与了环磷酸腺苷形成的诱导过程。DA的效力低于VIP,并以单相剂量反应曲线刺激环化酶活性。当一起检测时,这些刺激部分是非加性的,这意味着可能存在一个共同的腺苷酸环化酶池,可能受到这两种假定的神经递质的刺激。多巴胺能拮抗剂(+)-布他拉莫尔完全阻断了多巴胺能刺激,但对VIP诱导的刺激没有显著影响,这表明VIP与特定的VIP受体位点相互作用,这些位点与多巴胺能受体位点不同。此外,特异性D-2多巴胺能受体激动剂LY141865对腺苷酸环化酶活性没有抑制作用,这表明VIP敏感和DA敏感的腺苷酸环化酶系统之间的相互作用并非由兔视网膜中D-2受体介导的环化酶抑制所致。最后,在最大有效浓度下,DA和VIP在刺激环磷酸腺苷形成方面的效力低于氟化物或福斯可林,这表明该视网膜中可能也存在对DA和VIP不敏感的腺苷酸环化酶池。(摘要截短于250字)