Cholinergic facilitation of neurotransmission to the smooth muscle of the guinea-pig prostate gland

1 Functional experiments have been conducted to assess the effects of acety lcholine and carbachol, and the receptors on which they act to facilitate n eurotransmission to the stromal smooth muscle of the prostate gland of the guinea-pig. 2 Acetylcholine and carbachol (0.1 mu M-0.1 mM) enhanced contractions evoke d by trains of electrical field stimulation (20 pulses of 0.5 ms at 10 Hz e very 50 s with a dial setting of 60 V) of nerve terminals within the guinea -pig isolated prostate. In these concentrations they had negligible effects on prostatic smooth muscle tone. The facilitatory effects of acetylcholine , but not those of carbachol. were further enhanced in the presence of phys ostigmine (10 CIM). 3 The facilitatory effects of carbachol were unaffected by the neuropeptide Y Y, receptor antagonist BIBP 3226 ((R)-N-2-(diphenylacetyl)-N-[(4-hydroxy phenyl)methyl]-argininamide) (0.3 mu M, n = 3) or suramin (100 mu M, n = 5) . Prazosin (0.1 mu M, n = 5) and guanethidine (10 mu M, n = 5) alone and in combination (n = 4), reduced responses to field stimulation and produced r ightward shifts of the log concentration-response curves to carbachol. 4 The rank orders of potency of subtype-preferring muscarinic receptor anta gonists in inhibiting the facilitatory actions of acetylcholine and carbach ol were: pirenzepine > HHSiD (hexahydrosiladifenidol) > pF-HHSiD (para-fluo ro-hexahydrosiladifenidol) greater than or equal to himbacine, and pirenzep ine > HHSiD > himbacine greater than or equal to pF-HHSiD, respectively. Th ese profiles suggest that muscarinic receptors of the M-1-subtype mediate t he facilitatory effects of acetylcholine and carbachol on neurotransmission to the smooth muscle of the guinea-pig prostate.