Adenylate cyclase sensitivity to catecholamines and forskolin in rat pia-arachnoid and cerebral microvessels.
Adenylate cyclase in homogenates of perfused pia-arachnoid from the rat brain displayed a sensitivity for activation by dl'isoproterenol, l'epinephrine, l'norepinephrine (NE) and fenoterol that was greater than shown by partial beta2 adrenergic agonists (metaproterenol and salbutamol), or partial beta1 adrenergic agonists (tazolol and dobutamine) and an alpha adrenergic agonist (phenylephrine). The addition of the quanosine triphosphate (GTP) analog, Gpp(NH)p(5'-guanylyl imidodiphosphate) to the enzyme preparations resulted in an increased ability of all agents (except tazolol) to activate adenylate cyclase. The agent, forskolin, exerted a very potent activation of the catalytic site of adenylate cyclase in both pia-arachnoid and cerebral microvessels (capillary fraction). The order of potency for adrenergic antagonists to inhibit NE-induced stimulation of the pial enzyme was: propranolol (mixed beta) greater than butoxamine (beta2) greater than phentolamine (alpha1) greater than practolol (beta1). Subchronic injections of reserpine to rats resulted in a pial enzyme that was hyper-responsive to NE and isoproterenol. Similarly, the capillary enzyme displayed an enhanced activity to NE and dopamine (DA). Both high and low Km forms of cyclic AMP (cAMP) phosphodiesterase were detected in developing and adult pia-arachnoid and capillaries. The addition of a calmodulin fraction plus calcium ions did not elicit activation of the high Km enzyme. Moreover, adenylate cyclase during development was sensitive to activation by NE and forskolin. Thus, the pia-arachnoid possesses an adenylate cyclase receptor-coupled system with a mixed response to catecholamines, but which is primarily beta2 in nature. In addition, this system, as well as the capillaries, possesses a capacity to respond to manipulation of monoamine levels.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001099:Arachnoid / Q000098:blood supply*; D001921:Brain / Q000098:blood supply*; D002395:Catecholamines / Q000494:pharmacology*; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology
D002395:Catecholamines; D004224:Diterpenes; D013565:Sympatholytics; D005576:Colforsin; D012110:Reserpine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D007545:Isoproterenol