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)

Peptide YY (PYY), found in intestinal endocrine cells, and neuropeptide Y (NPY), a structural analogue of PYY found in neurons, inhibit gastric, pancreatic, and intestinal fluid and electrolyte secretion. We examined the effects of these peptides on dispersed chief cells from guinea pig stomach. PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion. These inhibitory peptides did not alter pepsinogen secretion caused by cholecystokinin, carbamylcholine, A23187, 8-bromo-cAMP, or a phorbol ester. The inhibitory effects of PYY on chief cell cAMP production occurred within 30 s, were independent of phosphodiesterase activity, and did not affect the actions of cholera toxin. However, the inhibitory effects of PYY were abolished when chief cells were preincubated with pertussis toxin, an agent that uncouples inhibitory guanine nucleotide binding (G) proteins from their receptors. In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP. PYY-induced attenuation of chief cell adenylate cyclase activity appears to involve activation of inhibitory G proteins.
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PMID:Actions of peptide YY and neuropeptide Y on chief cells from guinea pig stomach. 164 73

The pathway by which peptide YY inhibits upper gastrointestinal motility is largely unknown and prompted this investigation. Muscle tension and [3H]acetylcholine release studies were performed on isolated muscle strips and slices obtained from the guinea pig stomach. Peptide YY [0.1-1000 nmol/L; concentration of half-maximal effect (EC50), 6 nmol/L] caused concentration-dependent relaxation of longitudinally oriented muscle strips that was unaffected by hexamethonium but was blocked by atropine and tetrodotoxin, suggesting that the peptide inhibited postganglionic cholinergic neurotransmission. In addition, peptide YY (1 mumol/L) reduced by 42% +/- 6% electrically stimulated muscle contractions that were blocked by atropine and tetrodotoxin, providing additional evidence that the peptide inhibits release of acetylcholine. Next, the effect of peptide YY on potassium-evoked release of [3H]acetylcholine and whether the peptide inhibits cyclic adenosine monophosphate-dependent release of acetylcholine were examined. Peptide YY (1 mumol/L) inhibited KCl (35 mmol/L)-evoked release of [3H]acetylcholine by 58% +/- 6%. The inhibitory action of peptide YY was unaffected by antagonists for dopamine-2, alpha-2, and opiate receptors that are known to mediate presynaptic inhibition. In addition, peptide YY reduced half-maximal forskolin and cholera toxin-evoked release of acetylcholine by 45% +/- 6% and 42% +/- 8%, respectively, suggesting that the peptide can inhibit cyclic adenosine monophosphate-dependent release of acetylcholine. This effect of peptide YY was reversed by pertussis toxin which prevents activation of the inhibitory guanine nucleotide binding protein coupled to adenylate cyclase. In summary, peptide YY inhibited basal and stimulated cholinergic neurotransmission in the guinea pig stomach. In addition, peptide YY antagonized cyclic adenosine monophosphate-mediated release of acetylcholine through a pertussis toxin-sensitive mechanism.
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PMID:Mechanism of action of peptide YY to inhibit gastric motility. 184 99