Sulfhydryl G proteins and phospholipase A(2)-associated G proteins are involved in adrenergic signal transduction in the rat pineal gland.
The rat pineal gland with its circadian noradrenaline-regulated melatonin rhythm is an excellent model for studying adrenergic signal transduction with respect to cAMP and cGMP formation. The stimulatory G(s) proteins play a well-established role in this process. In contrast, the potential roles of the inhibitory G(i) proteins, the functionally unclear other G(o) proteins, and a number of G protein subtypes are not known. The present study examines the effects on beta(1)- and beta(1)-plus-alpha(1)-stimulated cAMP and cGMP formation of a number of G protein modulators in rat pinealocyte suspension cultures. The effects of the nitric oxide donor sodium nitroprusside on cGMP were also examined. The results showed that drugs that activate G proteins of the G(i)/G(o) family, i.e., pertussis toxin, mastoparan, and compound 48/80, had no effect on unstimulated, isoproterenol (beta(1))-stimulated, or combined isoproterenol/phenylephrine (beta(1)-plus()-alpha(1))-stimulated cAMP and cGMP accumulation. However, in this experimental paradigm, the inhibitors of sulfhydryl G proteins (N-ethylmaleimide) and those of phospholipase A2-related G proteins (isotetrandrine) exerted a clear inhibitory effect. Sodium-nitroprusside-stimulated cGMP accumulation was also inhibited. These results confirm a previous report that members of the G(i)/G(o) family, which are present in the rat pineal gland, do not play a major role in adrenergic signal transduction. The new finding that sulfhydryl G proteins and phospholipase A2-associated G proteins exert a clear stimulatory effect on adrenergic signal transduction suggests that they are subtypes of G(s) proteins.
Gupta
B B
BB
Department of Anatomy, Johannes Gutenberg University, Mainz, D-55099, Germany.
Spessert
R
R
Rimoldi
S
S
Vollrath
L
L
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis / Q000378:metabolism; D044182:Benzylisoquinolines; D000242:Cyclic AMP / Q000032:analysis / Q000096:biosynthesis; D006152:Cyclic GMP / Q000032:analysis / Q000096:biosynthesis; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010455:Peptides; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D054467:Phospholipases A2; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000470:Alkaloids; D044182:Benzylisoquinolines; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011941:Receptors, Adrenergic; D013439:Sulfhydryl Reagents; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D009599:Nitroprusside; D010656:Phenylephrine; C009438:tetrandrine; D009569:Nitric Oxide; D003189:p-Methoxy-N-methylphenethylamine; C037500:mastoparan; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D007545:Isoproterenol; D005033:Ethylmaleimide