Adenylate cyclase negative coupling

AC = adenylate cyclase (-) = negatively coupled (+) = positively coupled PI = phospholipase coupled. Currently accepted names are taken from Hoyer et al. (8). 

Wojcik, W. J. and Neff, N. H. (1984) Gamma-aminobutyric acid B receptors are negatively coupled to adenylate cyclase in brain and in the cerebellum these receptors may be associated with granule cells. Mol. Pharmacol. 25, 24-28. 

Yocca ED, Iben L, Meller E Lack of apparent receptor reserve at postsynaptic 5-hydroxytryptamine lA receptors negatively coupled to adenyl cyclase activity in rat hippocampal membranes. Mol Pharmacol 41 1066-1072, 1992 Yoney TH, Pigott TA, L Heureux F, et al. Seasonal variation in obsessive-compulsive disorder preliminary experience with light treatment. Am J Psychiatry 148 1727-1729, 1991... 

In the spinal cord, a2-agonists act on receptors located on the terminals of primary afferent fibers in the dorsal horn substantia gelatinosa to reduce nociceptive transmission by inhibiting the release of glutamate and substance P (Collin et al., 1994 Hamalainen and Pertovaara, 1995) (see Fig. 2). These receptors appear to be primarily of the a2A subtype which is negatively coupled to adenylate cyclase (Lakhlani et al., 1997 see Millan, 1999 but see Sawamura et al., 2000, and references therein for a discussion of the possible involvement of other a2-receptor subtypes in antinociception). Like activation of p-opioid receptors, the activation of a2-receptors increases the potassium conductance of the cells bearing these receptors, thus reducing cellular excitability. 

It is well know that /3-adrenoceptors couple to adenylate cyclases to activate a protein kinase A (PKA), but no direct evidence exists for the involvement of the /3-adrenoceptor-PKA signaling pathway in the affective component of pain. Thus, we examined the effect of intra-vBNST administration of a selective PKA inhibitor on isoproterenol- and pain-induced aversion. CPA induced by the intra-vBNST injection of isoproterenol was reversed by the coinjection of Rp-cyclic adenosine monophosphorothioate (Rp-cAMPS), a selective PKA inhibitor. Furthermore, intra-vBNST injection of Rp-cAMPS dose-dependently attenuated the F-CPA. These data suggest that PKA activation within the vBNST via the enhancement of /3-adrenergic transmission is important for the negative affective component of pain (Fig. 3). 

The dopamine receptor in the anterior pituitary gland is negatively coupled to adenylate cyclase... 

Since cyclic AMP derivatives and inhibitors of cyclic nucleotide phosphodiesterase stimulate prolactin release (17, 37, 38) and dopamine is a potent inhibitor of prolactin secretion (1, ly 39), it is not surprising that the catecholamine does not stimulate the adenylate cyclase system. On the contrary, the data summarized above show that the pituitary DA receptor is negatively coupled to adenylate cyclase. The pituitary DA receptor is thus a typical DA -receptor (40, 41). In view of the multiplicity of factors involved in the control of prolactin secretion, including sex steroids, it is likely that mechanisms other than cyclic AMP are involved (39, 42). It does however appear that inhibition of cyclic AMP formation by dopamine is a key element in a multifactorial control system responsible for the fine tuning of prolactin secretion. 

It has in fact been convincingly demonstrated that the anterior pituitary dopamine receptor is negatively coupled to adenylate cyclase in both tumoral (26), and normal (54) adenohypophysial tissue. Thus, the adenohypophysis cannot be taken, as originally proposed (36), as example of a receptor not coupled to adenylate cyclase. Moreover, it is well known that some dopaminergic responses appear independent of cyclic AMP (74, 75, 76). In order to take into account all the available data, it appears preferable to use the terminology DA+, DA and DA. (54, Fig. 4). Other advantages of this terminology are its clear separation from the nomen-... 

Angers A, Storozhuk MV, Duchaine T, Castellucci VF, DesGroseillers L. Cloning and functional expression of an Aplysia 5-HT receptor negatively coupled to adenylate cyclase. JNeurosci 1998 18 5586-5593. 

Bouhelal R, Smounya L, Bockaert J. 5-HTm receptors are negatively coupled with adenylate cyclase in rat substantia nigra. Eur J Pharmacol 1988 151 189-196. 

The 5-HT1B receptors are predominantly localized at the presynaptic level, they are coupled negatively to adenylate cyclase, and their activation by selective agonists induces a decrease in the forskolin-stimulated adenylate cyclase (156) for review, see ref. 157. Consequently, their activation reduces neurotransmitter release (see below). 

Anand-Srivastava, M.B. 1989. Angiotensin II receptors negatively coupled to adenylate cyclase in rat myocardial sarcolemma. Involvement of inhibitory guanine nucleotide regulatory protein. Biochem. Pharmacol. 38 489-496. 

Enjalbert A, Bockaert J (1983) Pharmacological characterization of the D2 dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary. Mol Pharmacol 23 576-584. 

Receptor Populations. Seven major families or populations of serotonin receptors have been identified S-HTi-S-HTy receptors. Several of these populations are divided into subpopulations (119-121). For example, 5-HT, (5-HT,a, 5-HTib, 5-HTib, 5-HT, S-HT f) and 5-HT, (5-HT, 5-HT, S-HTac) receptors represent serotonin receptor populations for which subpopulations exist. With the exception of the 5-HT, receptors, which are directly linked to an ion channel, all the other 5-HT receptors belong to the G-protein-coupled superfamily of receptors. 5-HT, receptors are negatively coupled to an adenylate cyclase second-messenger system, whereas the 5-HT 5-HT and 5-HT, receptors are positively coupled. 5-HT, receptors are coupled to a phosphatidylinositol second-messenger system. There is evidence that 5-HT, receptors and 5-HT, receptors are involved in depression. Certain of the other 5-HT receptors may also play a role in depression and there is evidence for functional interactions between 5-HT receptors. 

Two types of cannabinoid receptor have so far been identified (reviewed in Howlett et al. 2002). These are CBi, cloned in Tom Bonner s laboratory in the USA in 1990, and CB2, cloned by Sean Munro in the UK in 1993. Both these receptors are coupled through Gi/o proteins, negatively to adenylate cyclase and positively to mitogen-activated protein kinase. CBi receptors are also coupled through Gi/o proteins, positively to A-type and inwardly rectifying potassium channels and negatively to N-type and P/Q-type calcium channels and to D-type potassium channels. In addition, there are reports that CBi and CB2 receptors can enhance intracellular free Ga concentrations (Fan and Yazulla 2003 Rubovitch et al. 2002 Sugiura et al. 1996, 1997, 2000). It is unclear whether this enhancement is Gi/o... 

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