vasoactive-intestinal-peptide and preclamol

The abilities of dopamine (DA) and the partial DA D2 receptor agonist (-)-(3-hydroxyphenyl)-N-n-propylpiperidine, (-)-3-PPP, to suppress prolactin (PRL) release induced by any of five different PRL secretagogues in GH4C1 cells transfected with the human D2 receptor (short isoform) were investigated. Whereas DA reduced the response to all five secretagogues. (-)-3-PPP reduced the response to vasoactive intestinal peptide (VIP) and thyrotropin-releasing hormone (TRH), but not to high medium potassium (K+) or to the potassium channel antagonist tetraethylammonium (TEA). (-)-3-PPP tended to reduce the PRL release induced by the Ca2+ channel agonist BAY K-8644 (BAY); however, this effect of the partial agonist was modest and not significant. Whereas the effects of both DA and (-)-3-PPP on the PRL response to VIP and TRH were counteracted by co-incubation with the D2 antagonist raclopride, the effects of DA on the PRL response to K+, BAY, and TEA were antagonized by co-incubation with either raclopride or (-)-3-PPP. The results show that, at a given receptor density, the intrinsic activity of a partial D2 agonist with respect to D2-mediated suppression of PRL release may vary from agonism to antagonism depending on which intracellular transduction systems that are being concomitantly activated.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Cell Line; Dopamine; Dopamine Agonists; Humans; Piperidines; Potassium; Prolactin; Receptors, Dopamine D2; Tetraethylammonium; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide

The modulation of 3,4-dihydroxyphenylethylamine (dopamine, DA) synthesis and release in rabbit retina in vitro by high K+; adenylate cyclase activators such as forskolin, 2-chloroadenosine, vasoactive intestinal polypeptide (VIP); and the putative DA autoreceptor agonist N-n-propyl-3-(3-hydroxyphenyl) piperidine (3-PPP) has been investigated. Incubation of retinas in 50 mM K+ resulted in the activation of tyrosine hydroxylase (TH). Activation did not require the presence of extracellular Ca2+. K+ 50 mM also induced a Ca2+-dependent release of DA. Forskolin 50 microM stimulated TH but 100 microM 2-chloroadenosine and 650 nM VIP did not. Individually, (+)-3-PPP, (-)-3-PPP, and (+/-)-3-PPP reduced DA synthesis and increased its release. The effects of (+/-)-3-PPP were dose-dependent and did not require the presence of extracellular Ca2+. The activation of TH induced by 50 mM K+, but not that induced by 50 microM forskolin, was abolished by 100 microM (+/-)-3-PPP.

Topics: 2-Chloroadenosine; Adenosine; Adenylyl Cyclases; Animals; Calcium; Colforsin; Dopamine; Enzyme Activation; Female; Male; Piperidines; Potassium; Rabbits; Retina; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

The effects of some dopaminomimetics on VIP levels in peripheral venous blood of conscious dogs were analysed with a radioimmunoassay. The dopamine D2 agonist pergolide, like apomorphine and bromocriptine, increased VIP levels. The putative DA autoreceptor agonist 3PPP, as well as the D1 agonist SK&F 38393 were devoid of action. The D1 antagonist SCH 23390 did not abolish the effect of apomorphine. It is suggested that monitoring of VIP levels could be an interesting screening test for activity at D2 receptors. Amphetamine did not modify VIP levels suggesting that DA neurons are not involved in the mechanism leading to a release of VIP. The VIP response to apomorphine was not suppressed by an infusion of somatostatin. Decreasing blood pressure with nitroglycerin or with the adrenergic antagonist prazosin did not release VIP. The mechanism by which administration of dopaminomimetics lead to a release of VIP is further discussed.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amphetamine; Animals; Apomorphine; Benzazepines; Dogs; Ergolines; Nitroglycerin; Pergolide; Piperidines; Prazosin; Receptors, Dopamine; Somatostatin; Vasoactive Intestinal Peptide