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  • Title: Beta-adrenoceptor-mediated inhibition of alpha 1-adrenoceptor-mediated and field stimulation-induced contractile responses in the prostate of the guinea pig.
    Author: Haynes JM, Hill SJ.
    Journal: Br J Pharmacol; 1997 Nov; 122(6):1067-74. PubMed ID: 9401771.
    Abstract:
    1. The prostate of the guinea pig responds to electrical field-stimulation (2 s trains, 0.1 ms pulses at 3-60 Hz, supramaximal voltage) with contractile responses. At 18 Hz these responses were inhibited (82 +/- 2%) by the L-type Ca2+ channel blocker, nifedipine (10 microM) and (by 100%) by the neurotoxin, tetrodotoxin (500 nM). The alpha 1A-selective adrenoceptor antagonist, 5-methylurapidil, inhibited responses to field stimulation in the absence and presence of nifedipine (10 microM) with -log molar (p) IC50 (+/- s.e. mean) values of 7.95 +/- 0.14 and 7.01 +/- 0.07, respectively. 2. The non-selective beta-adrenoceptor agonist, isoprenaline, reduced (56 +/- 8%) field stimulation induced contractile responses (pEC50 6.91 +/- 0.11). The non-selective beta-adrenoceptor antagonist propranolol (50 nM) and the beta 1-adrenoceptor selective antagonist, atenolol (3 microM), but not the beta 2-adrenoceptor antagonist ICI 118,551 ((+/-)-1 -[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxyl]-3-[1-methylethyl)amino ]-2-butanol HCl; 100 nM) antagonized this effect (apparent pKB values 8.44 +/- 0.22 and 6.92 +/- 0.21, respectively) indicating an effect mediated through beta 1-like adrenoceptors. In the presence of nifedipine (10 microM) isoprenaline (up to 10 microM) did not inhibit the remaining response to field-stimulation. 3. Phenylephrine elicited contractile responses (pEC50 4.47 +/- 0.30) from preparations of guinea pig prostate which were reduced (63 +/- 25%) by nifedipine (10 microM). This response was antagonized by 5-methylurapidil (100 nM, apparent pKB 8.24 +/- 0.33), but was not affected by preincubation chloroethylclonidine (50 microM, 30 min). Responses to phenylephrine (30 microM) were inhibited (by up to 52 +/- 5%) by isoprenaline (pIC50 6.40 +/- 0.35, the beta 2-adrenoceptor selective agonist, salbutamol was weakly effective). Propranolol (300 nM), ICI 118,551 (100 nM) and atenolol (3 microM) shifted isoprenaline concentration-response curves to the right (apparent pKB +/- s.e. values 7.68 +/- 1.10; 8.00 +/- 0.72 and 6.62 +/- 0.95, respectively). In the presence of nifedipine (10 microM) responses to phenylephrine (30 microM,) were inhibited (by up to 51 +/- 4%) by isoprenaline (pIC50 6.88 +/- 0.17): propranolol (300 nM) and ICI 118,551 (100 nM), but not atenolol (3 microM) antagonized this effect (apparent pKB values 8.85 +/- 1.53 and 8.35 +/- 1.18, respectively). Thus beta 1-like and beta 2-like adrenoceptors may be involved in the isoprenaline-stimulated inhibition of phenylephrine concentration-response curves. 4. Phenylephrine stimulated [3H]-inositol phosphate accumulation (pEC50 4.47 +/- 0.83), an effect insensitive to chloroethylclonidine pre-treatment (50 microM, 30 min) and to nifedipine (10 microM), but inhibited by 5-methylurapidil (apparent pKD 7.90 +/- 0.22). Isoprenaline (up to 1 microM) did not affect the phenylephrine-stimulated maximal increase in [3H]-inositol phosphates but did increase [3H]-cyclic adenosine monophosphate ([3H]-cAMP) accumulation (pEC50 6.77 +/- 0.66); propranolol (30 nM) and ICI 118,551 (110 nM), but not atenolol (up to 3 microM), antagonized this effect. These responses may therefore be mediated through beta 2-like adrenoceptors. 5. These results show that the alpha 1-adrenoceptor mediated and field stimulation-induced contractions of the guinea pig prostate are partly dependent upon intracellular and extracellular sources of Ca2+. We conclude that both beta 1- and beta 2-like adrenoceptors inhibit responses to phenylephrine in the prostate of the guinea pig. The beta 1-like adrenoceptor-mediated inhibition of these responses is evident upon the field stimulation-induced and nifedipine-sensitive component of the response to phenylephrine and may not involve the activation of adenylyl cyclase. The beta 2-like adrenoceptor may inhibit both nifedipine sensitive and insensitive components of the response to phenylephrine, possibly through the activation of adenylyl cyclase, but not through the i
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