Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Completion of the process of maturation of spermatozoa (capacitation) occurs in the female genital tract. As a result, spermatozoa acquire hypermobility and the capability for the acrosomal reaction, which determine their fertility. There exist data that participating in these processes are the adenylyl cyclase and guanylyl cyclase signaling systems that are present in human and mammalian spermatozoa. The goal of the present work to characterize these systems in the human ejaculate spermatozoa (ES) and in the human fertile spermatozoa (FS) isolated by the density gradient centrifugation. In the FS homogenate the basal activity of adenylyl cyclase (AC) activity was significantly higher that in ES: 47 +/- 5 vs 28 +/- 3 pmol cAMP/min per mg of protein, respectively. At the same time, the AC-stimulating effects of non-hormonal activators of AC forms (NaHCO3, Mn2+, forskolin, and non-hydrolysable GTP analogue - GppNHp) were lower as compared with ES. The AC activity in ES were stimulated by isoproterenol, serotonin, PACAP-38, and, to the letter degree, by noradrenalin and adenosine. Among the AC-inhibiting hormones, adenosine alone decreased the enzyme activity. In FS, on the contrary, the AC-inhibiting effects of adenosine, noradrenaline, and serotonin were clearly expressed, whereas the stimulatory effects of these hormones were attenuated or absent. The basal activity of guanylyl cyclase (GC) in the ES and FS homogenates amounted to 27 +/- 3 and to 21 +/- 2 pmol cGMP for 1 min per 1 mg protein, respectively, and was significantly increased in the presence of 10 mM Mn2+. The GC-stimulating effects of natriuretic peptides - atrial natriuretic peptide (ANP) and the C-type natriuretic peptide (CNP)--activators of the GC receptor forms, were in ES significantly higher than in FS, the ANP effect being more pronounced as compared with CNP. The obtained data indicate multiplicity of the cAMP- and cGMP-dependent signal cascades regulating fertility of human spermatozoa. It has been established that sensitivity of AC and GC to hormones in the total ES pool and in the supermobile FS fraction isolated by centrifugation differs essentially, which is to be taken into account when using FS for auxiliary reproductive technologies.
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PMID:[Regulatory properties of adenylyl and guanylyl cyclases in human spermatozoa]. 2366 79


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