Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vasodilator effects of pituitary adenylate cyclase activating polypeptide (PACAP-27) are subject to tachyphylaxis in rats treated with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). This study examined whether this tachyphylaxis is due to the loss of vasodilator potency of cAMP generated by activation of the G(s) protein-coupled PACAP receptors. Five successive treatments with PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats that were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in L-NAME (50 micromol/kg iv)-treated rats produced vasodilator responses of similar magnitude to those in saline-treated rats, whereas four subsequent injections produced progressively and markedly smaller responses. The hemodynamic effects of the membrane-permeable cAMP analog 8-(4-chlorophenylthiol)-cAMP (8-CPT-cAMP; 5-15 micromol/kg iv) were similar in L-NAME-treated rats and in L-NAME-treated rats that had received the five injections of PACAP-27. In addition, five injections of 8-CPT-cAMP (10 micromol/kg iv) produced pronounced vasodilator responses in saline- and L-NAME-treated rats that were not subject to the development of tachyphylaxis. These results suggest that a loss of biological potency of cAMP is not responsible for tachyphylaxis to PACAP-27 in L-NAME-treated rats. This tachyphylaxis may be due to the inability of the G(s) protein-coupled PACAP receptor to activate adenylate cyclase.
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PMID:Tachyphylaxis to PACAP-27 after inhibition of NO synthesis: a loss of adenylate cyclase activation. 1056 19

We investigated, in murine colon circular muscle, the role of adenosine 5'-triphosphate (ATP) and pituitary adenylate cyclase activating peptide (PACAP) as inhibitory neurotransmitters of the fast component of nerve-evoked inhibitory junction potential (fast IJP). Fast IJP was antagonised by apamin or suramin, abolished by desensitisation with the P2Y receptor agonist, adenosine 5'-O-2-thiodiphosphate (ADPbetaS), unaffected by desensitisation with P2X receptor agonist, alpha,beta-methylene ATP (alpha,beta-meATP), and reduced by PACAP-(6-38), a PACAP receptor antagonist. ATP induced membrane hyperpolarization resistant to tetrodotoxin, N(omega)-nitro-L-arginine methyl ester (L-NAME) or PACAP-(6-38), but antagonised by apamin, suramin, P2X and P2Y receptor desensitisation. PACAP-(1-27) caused membrane hyperpolarization antagonised by PACAP-(6-38), apamin and P2Y receptor desensitisation, reduced by tetrodotoxin, but not affected by L-NAME and by P2X receptor desensitisation. Therefore, in murine colon circular muscle, an ATP-like endogenous P2Y purinoceptor ligand is the final nonadrenergic, noncholinergic (NANC) inhibitory mediator involved in the generation of fast IJP. A neuromodulator role of PACAP in the inhibitory pathway is supposed.
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PMID:Neurotransmitters involved in the fast inhibitory junction potentials in mouse distal colon. 1255 80

We investigated the possibility that pituitary adenylate cyclase activating peptide (PACAP) has a role in the control of contractility in the mouse ileum. PACAP-(1-27) produced tetrodotoxin (TTX)-insensitive, concentration-dependent reduction of the amplitude of the spontaneous contractions of longitudinal muscle up to their complete disappearance. This effect was inhibited by PACAP-(6-38), PACAP receptor antagonist, and by apamin, blocker of small-conductance Ca2+-activated K+-channels. Nomega-nitro-L-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, reduced the PACAP-inhibitory response, and the joint application of apamin plus L-NAME produced additive effects. 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), inhibitor of NO-stimulated soluble guanylate cyclase, significantly reduced the effect of PACAP. Exogenous NO, given as sodium nitroprusside (SNP), induced a concentration-dependent suppression of the phasic contractions, which was unaffected by apamin but reduced by either PACAP-(6-38) or TTX. Neurally evoked muscular relaxation was deeply antagonised by L-NAME. PACAP-(6-38) induced a reduction of the response to EFS only in the absence L-NAME. In conclusion, our results suggest that PACAP controls smooth muscle contractility, acting directly on the muscle cells through PACAP-27 preferring receptors coupled to apamin-sensitive Ca2+-dependent K+-channels and indirectly through the stimulation of NO production. In turn, NO would stimulate the release of PACAP from inhibitory neurones.
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PMID:Interplay between PACAP and NO in mouse ileum. 1497