Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical evidence is presented for selective decreases in biogenic amine receptor systems with age in the rabbit. Dopamine-stimulated adenylate cyclase activity in striatum, hypothalamus, frontal cortex, and anterior limbic cortex declined by about 50% as rabbits aged from less than 1 to 5 years of age. Similar decreases were found for histamine-stimulated activity in hypothalamus and the cortical regions. These changes were in maximal response rather than in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and Gpp(NH)p-stimulated activity in these regions were not altered with age. In addition, with age the number of binding sites for [3H]spiroperidol, a dopamine antagonist, decreased by 30--40% without change in ligand affinity in striatum and limbic cortex. These changes in striatum and cortex occurred in the absence of decreases in either dopamine concentration or choline acetylase activity. It is proposed that selective age-dependent decreases in the functional number of biogenic amine receptors occur in the absence of, or independent from neuronal cell loss, possibly by a mechanism of desensitization. These changes occurred in brain regions that in man are thought to be of importance in the age-related loss of cerebral function.
 ...
PMID:Aging and monoamine receptors in brain. 21 50

Evidence for selective decreases in biogenic amine receptor function with age in the rabbit has been obtained. Dopamine-stimulated adenylate cyclase activity in the striatum (caudate-putamen) of rabbit brain declined by about 50 percent as rabbits aged from less than 1 to 4 to 5 years of age. Similar decreases in transmitter-stimulated adenylate cyclase activity were found for histamine as well as for dopamine and norepinephrine in hypothalamus, frontal cortex and anterior limbic cortex. Isoproterenol-stimulated activity was also decreased with age in frontal cortex. These changes appeared to represent decreases in maximal response and not alteration in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and transmitter-independent (basal or Gpp(NH)p-stimulated) activity in each of the regions studied were not altered with age. Dopamine receptors in striatum directly assessed by measurement of [3H]-spiroperidol binding revealed a comparable decrease in the number of binding sites without change in ligand affinity. Preliminary data also indicated decreased spiroperidol binding sites in the cortical regions of older animals. These changes in striatum and cortex were evident in the absence of decreases in either dopamine content or choline acetylase activity, an activity presumed to be present in neurons containing dopamine receptors. It is proposed that selective age-dependent decreases in postsynaptic biogenic amine receptor content occur in the absence of, or independent from, neuronal cell loss, possibly by a mechanism involving receptor desensitization. These changes occur in the animal model in those brain regions which in man are thought to be of importance in the loss of cerebral function that is found with senscence.
 ...
PMID:Biogenic amine-stimulated adenylate cyclase and spiroperidol-binding sites in rabbit brain: evidence for selective loss of receptors with aging. 75 89

Dopamine-stimulated adenylate cyclase activity in striatum and both dopamine- and histamine-stimulated adenylate cyclase activity in hypothalamus, frontal cortex and anterior limbic cortex declined by about 50% as rabbits aged from 5.5 months to 5.5 years of age. These changes were primarily in maximal response to amine although an additional component involving decreased affinity in the case of dopamine may also be present. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and guanyl-5'-yl-imidodiphosphate (Gpp(NH)p)-stimulated activity in these regions were not altered with age. There was no measurable decrease in the old animals in either dopamine or norepinephrine concentration in striatum, anterior limbic cortex or retina, or in choline acetylase activity or [3H]quinuclidinylbenzilate binding in striatum, anterior limbic cortex or frontal cortex. It is proposed that selective age-dependent decreases in transmitter receptors coupled to adenylate cyclases occur in the absence of or independent from neuronal cell loss, as evidenced by the retention of the other biochemical markers.
 ...
PMID:Evidence for selective loss of brain dopamine- and histamine-stimulated adenylate cyclase activities in rabbits with aging. 737 78