Pharmacological modulation of the pontine micturition center.
Previous studies have indicated that an area of the rostral pontine tegmentum known as the 'pontine micturition center' (PMC) plays an essential role in the regulation of lower urinary tract function. The present pharmacologic experiments were conducted on either decerebrate unanesthetized or chloralose anesthetized cats to identify the location of the PMC and to examine the neurotransmitter mechanisms controlling micturition. Microinjections of excitatory and inhibitory amino acids were made at stereotaxic coordinates P1 to P3, L2 to L3, H0 to H-4 where electrical stimulation with trains of pulses (2-30 V, 80-120 Hz and 50-300 ms train duration) elicited short latency (less than 2 s) bladder contractions or voiding. Injections of L-glutamate (L-GLUT) (20-130 nmol) or DL-homocysteic acid (DLH) (20-100 nmol) into the region of the locus coeruleus or parabrachial nucleus elicited voiding as well as an increase in the frequency or amplitude of isovolumetric bladder contractions. In some anesthetized animals, L-GLUT and DLH also had mixed excitatory-inhibitory or pure inhibitory effects. Injections of muscimol (9-70 nmol) depressed rhythmic bladder activity, increased the bladder volume for inducing micturition or completely abolished the voiding induced by bladder filling. The inhibitory effects of muscimol were reversed by microinjections of bicuculline methiodide (BCMI) (3-22 nmol). Injections of BCMI (1-1.5 nmol) into untreated cats stimulated bladder activity and lowered the bladder volume for inducing micturition. It is concluded that: (1) neurons in the rostral pons are an essential component of the micturition reflex pathway, (2) several populations of neurons located in the region of the locus coeruleus complex and parabrachial nucleus contribute to the functions of the PMC, and (3) PMC neurons are under a tonic GABAergic inhibitory control which regulates the micturition threshold and in turn regulates bladder capacity.
Department of Pharmacology, University of Pittsburgh, School of Medicine, PA 15261.
B S
BS
Mallory
J R
JR
Roppolo
W C
WC
de Groat
D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002415:Cats; D003655:Decerebrate State; D004558:Electric Stimulation; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D011149:Pons / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D014521:Urethra / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology; D014554:Urination / Q000502:physiology*
D000596:Amino Acids; D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D006710:Homocysteine; C007956:homocysteic acid; D009118:Muscimol; D018698:Glutamic Acid; D001640:Bicuculline